FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Landry, JC Feng, Y Cohen, SJ Staley, C Whittington, R Sigurdson, ER Nimeiri, H Verma, U Prabhu, RS Benson, AB AF Landry, J. C. Feng, Y. Cohen, S. J. Staley, C. Whittington, R. Sigurdson, E. R. Nimeiri, H. Verma, U. Prabhu, R. S. Benson, A. B. TI Phase II Study of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: ECOG 3204 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Landry, J. C.; Staley, C.; Prabhu, R. S.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Feng, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, S. J.; Sigurdson, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Whittington, R.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Nimeiri, H.; Benson, A. B.] Northwestern Univ, Chicago, IL 60611 USA. [Verma, U.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S144 EP S145 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900358 ER PT J AU Laufer, M ter Veer, A Bekaii-Saab, T Cohen, S Lai, L Schrag, D Skibber, JM Small, W Wilkinson, N Goodman, KA AF Laufer, M. ter Veer, A. Bekaii-Saab, T. Cohen, S. Lai, L. Schrag, D. Skibber, J. M. Small, W. Wilkinson, N. Goodman, K. A. TI Neoadjuvant Radiation Therapy Use in Locally Advanced Rectal Cancer at National Comprehensive Cancer Network (NCCN) Centers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Laufer, M.; Goodman, K. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [ter Veer, A.; Lai, L.] City Hope Canc Ctr, Duarte, CA USA. [Bekaii-Saab, T.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Bekaii-Saab, T.] Solove Res Inst, Columbus, OH 43210 USA. [Cohen, S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Skibber, J. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Small, W.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Wilkinson, N.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S348 EP S348 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901063 ER PT J AU Lawton, CA Shook, S Smith, M Tripp, P Shah, AB Martin, A Kim, HE Tai, P Nabid, A Kachnik, LA AF Lawton, C. A. Shook, S. Smith, M. Tripp, P. Shah, A. B. Martin, A. Kim, H. E. Tai, P. Nabid, A. Kachnik, L. A. TI RTOG Protocol 05-18: A Phase III Randomized Trial to Evaluate the Efficacy of Zoledronic Acid for the Prevention of Osteoporosis and Associated Fractures in Patients Receiving Radiation Therapy (RT) and Long-term Luteinizing Hormone-releasing Hormone (LHRH) Agonist for High-grade and/or Locally Advanced Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lawton, C. A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Shook, S.] RTOG Stat Ctr, Philadelphia, PA USA. [Smith, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tripp, P.] Zablocki VA Med Ctr, Milwaukee, WI USA. [Shah, A. B.] York Canc Ctr, York, PA USA. [Martin, A.] L Hotel Dieu Quebec, Quebec City, PQ, Canada. [Kim, H. E.] Wayne State Univ, Detroit, MI USA. [Tai, P.] Allen Blair Canc Ctr, Regina, SK, Canada. [Nabid, A.] Ctr Hosp Univ Sherbrooke, Quebec City, PQ, Canada. [Kachnik, L. A.] Boston Med Ctr MBCCOP, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S369 EP S369 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901119 ER PT J AU Lee, AK Levy, LB Rossi, CJ Bush, DA Choi, S Mendenhall, NP Nguyen, QN Keole, S Zietman, AL Slater, JD AF Lee, A. K. Levy, L. B. Rossi, C. J. Bush, D. A. Choi, S. Mendenhall, N. P. Nguyen, Q. N. Keole, S. Zietman, A. L. Slater, J. D. TI Multi-institutional Patient-reported Quality of Life After Proton Therapy for Prostate Cancer Compared to Nontreated Men SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lee, A. K.; Levy, L. B.; Choi, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rossi, C. J.] Loma Linda Univ, Med Ctr, Scripps Proton Ctr, Loma Linda, CA USA. [Mendenhall, N. P.] Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. [Nguyen, Q. N.] USC, Los Angeles, CA USA. [Keole, S.] Radiat Med Associates, Oklahoma City, OK USA. [Zietman, A. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S646 EP S647 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902137 ER PT J AU Lee, LJ Newhouse, C Chen, Y Viswanathan, AN AF Lee, L. J. Newhouse, C. Chen, Y. Viswanathan, A. N. TI Nonserous Histology and Platinum-sensitivity are Prognostic in Localized Recurrent Ovarian Cancer Treated With Radiation Therapy (RT) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lee, L. J.; Newhouse, C.; Viswanathan, A. N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S96 EP S96 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900238 ER PT J AU Lester-Coll, N Goldhaber, SZ Sher, DJ D'Amico, AV AF Lester-Coll, N. Goldhaber, S. Z. Sher, D. J. D'Amico, A. V. TI Balancing Competing Risks of Recurrence and Death from High-risk Prostate Cancer Versus Cardiovascular Mortality in Men Treated With Hormonal Therapy: A Decision Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lester-Coll, N.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Goldhaber, S. Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA. [Sher, D. J.] Rush Univ, Dept Radiat Oncol, Med Ctr, Chicago, IL 60612 USA. [D'Amico, A. V.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S124 EP S124 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900309 ER PT J AU Lewis, J Li, R St James, S Yue, Y Berbeco, R Mishra, P AF Lewis, J. Li, R. St James, S. Yue, Y. Berbeco, R. Mishra, P. TI Fluoroscopic 3D Images Based on 2D Treatment Images Using a Realistic Modified XCAT Phantom SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lewis, J.; St James, S.; Yue, Y.; Berbeco, R.; Mishra, P.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Ctr, Sch Med, Boston, MA 02115 USA. [Li, R.] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S737 EP S737 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902378 ER PT J AU Lin, C Winey, B AF Lin, C. Winey, B. TI Shape Distribution-based 2D/3D Registration for Fast and Accurate 6 Degrees-of-Freedom Stereotactic Patient Positioning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Lin, C.] MIT, Cambridge, MA 02139 USA. [Lin, C.; Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S724 EP S724 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902346 ER PT J AU MacDonald, S Specht, M Isakoff, S Gadd, M Smith, B Adams, J Hickey, S Kooy, H Lu, H Taghian, AG AF MacDonald, S. Specht, M. Isakoff, S. Gadd, M. Smith, B. Adams, J. Hickey, S. Kooy, H. Lu, H. Taghian, A. G. TI Prospective Pilot Study of Proton Radiation Therapy for Invasive Carcinoma of the Breast Following Mastectomy in Patients With Unfavorable Anatomy - First Reported Clinical Experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [MacDonald, S.; Specht, M.; Isakoff, S.; Gadd, M.; Smith, B.; Adams, J.; Hickey, S.; Kooy, H.; Lu, H.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S113 EP S114 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900283 ER PT J AU Mailhot, R Rotondo, R Murphy, E Caruso, PA Fullerton, B Tarbell, NJ Yock, TI Merchant, TE Donahue, B MacDonald, SM AF Mailhot, R. Rotondo, R. Murphy, E. Caruso, P. A. Fullerton, B. Tarbell, N. J. Yock, T. I. Merchant, T. E. Donahue, B. MacDonald, S. M. TI A Consensus Atlas for Whole Ventricular Irradiation for Pediatric Germ Cell Tumors: Survey Results and Guidelines SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mailhot, R.] Washington Univ, Sch Med, St Louis, MO USA. [Rotondo, R.; Caruso, P. A.; Fullerton, B.; Tarbell, N. J.; Yock, T. I.; MacDonald, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Murphy, E.] Cleveland Clin, Cleveland, OH 44106 USA. [Merchant, T. E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Donahue, B.] Maimonides Hosp, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S65 EP S65 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900162 ER PT J AU Mak, KS Yan, Y Smith, MR Hanks, GE Brereton, HD Bauman, G Rosenthal, SA Zeitzer, KL Sandler, HM Efstathiou, JA AF Mak, K. S. Yan, Y. Smith, M. R. Hanks, G. E. Brereton, H. D. Bauman, G. Rosenthal, S. A. Zeitzer, K. L. Sandler, H. M. Efstathiou, J. A. TI Diabetes and Cardiovascular Mortality in Men With Locally Advanced Prostate Cancer: Updated Analysis From RTOG 92-02 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mak, K. S.] Harvard Radiat Oncol Program, Boston, MA USA. [Yan, Y.] RTOG Stat Ctr, Philadelphia, PA USA. [Smith, M. R.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hanks, G. E.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Brereton, H. D.] NE Radiat Oncol Ctr, Scranton, PA USA. [Bauman, G.] London Reg Canc Program, London, ON, Canada. [Rosenthal, S. A.] Radiol Associates Sacramento, Radiat Oncol Ctr, Sacramento, CA USA. [Zeitzer, K. L.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Sandler, H. M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. RI Bauman, Glenn/D-5986-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S94 EP S94 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900233 ER PT J AU Mak, RH Hunt, D Shipley, WU Efstathiou, JA Yan, Y Tester, WJ Hagan, MP Kaufman, DS Heney, NM Zietman, AL AF Mak, R. H. Hunt, D. Shipley, W. U. Efstathiou, J. A. Yan, Y. Tester, W. J. Hagan, M. P. Kaufman, D. S. Heney, N. M. Zietman, A. L. TI Long-term Outcomes After Bladder Preserving Combined Modality Therapy for Muscle-invasive Bladder Cancer: A Pooled Analysis of RTOG 8802, 8903, 9506, 9706, 9906, and 0233 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mak, R. H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hunt, D.; Yan, Y.] RTOG Stat Ctr, Philadelphia, PA USA. [Shipley, W. U.; Efstathiou, J. A.; Kaufman, D. S.; Heney, N. M.; Zietman, A. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tester, W. J.] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Hagan, M. P.] Virginia Commonwealth Univ, Richmond, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S121 EP S121 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900301 ER PT J AU Mak, RH Hunt, D Shipley, WU Jones, CU Lukka, HR Bahary, JP Souhami, L Husain, S Efstathiou, JA Sandler, HM AF Mak, R. H. Hunt, D. Shipley, W. U. Jones, C. U. Lukka, H. R. Bahary, J. P. Souhami, L. Husain, S. Efstathiou, J. A. Sandler, H. M. TI Acute and Late Urinary Toxicity After Radiation Therapy in Men With and Without an Intact Prostate Gland: A Secondary Analysis of RTOG 9408 and 9601 Suggesting This Toxicity is Not Due to Bladder Injury SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mak, R. H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hunt, D.] RTOG Stat Ctr, Philadelphia, PA USA. [Shipley, W. U.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jones, C. U.] Radiol Associates Sacramento, Sacramento, CA USA. [Lukka, H. R.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Lukka, H. R.] McMaster Univ, Hamilton, ON, Canada. [Bahary, J. P.] Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. [Souhami, L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Husain, S.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Sandler, H. M.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S14 EP S14 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900037 ER PT J AU Malone, S Eapen, L Kendal, W MacRae, R D'Amico, A Perry, G Bowen, J Malone, K Grimes, S AF Malone, S. Eapen, L. Kendal, W. MacRae, R. D'Amico, A. Perry, G. Bowen, J. Malone, K. Grimes, S. TI Preliminary Results of a Randomized Trial of Optimal Timing of Dose Escalated (76 Gy) Radiation and 6 months ADT in Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Malone, S.; Eapen, L.; Kendal, W.; MacRae, R.; Perry, G.; Malone, K.; Grimes, S.] Ottawa Hosp Canc Ctr, Ottawa, ON, Canada. [D'Amico, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bowen, J.] NE Canc Ctr, Sudbury, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S362 EP S362 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901101 ER PT J AU Margalit, DN Meisner, A Kasperzyk, JL Penney, KL Martin, NE Schoenfeld, JD Chan, JM Stampfer, MJ Giovannucci, E Mucci, LA AF Margalit, D. N. Meisner, A. Kasperzyk, J. L. Penney, K. L. Martin, N. E. Schoenfeld, J. D. Chan, J. M. Stampfer, M. J. Giovannucci, E. Mucci, L. A. TI Genetic Variation in the Antioxidant Gene Superoxide Dismutase 2 (SOD2) and Response to Radiation Therapy (RT) for Prostate Cancer (PCa) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Margalit, D. N.; Martin, N. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Meisner, A.; Kasperzyk, J. L.; Penney, K. L.; Giovannucci, E.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Schoenfeld, J. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Chan, J. M.] Univ Calif San Francisco, San Francisco, MA USA. [Stampfer, M. J.; Mucci, L. A.] Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Boston, MA 02115 USA. RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S58 EP S58 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900146 ER PT J AU McCormick, B Ottesen, R Hughes, M Javid, S Khan, S Mortimer, J Niland, J Weeks, J Edge, S AF McCormick, B. Ottesen, R. Hughes, M. Javid, S. Khan, S. Mortimer, J. Niland, J. Weeks, J. Edge, S. TI Impact of Guideline Changes in the Elderly With Early Breast Cancer (BC): Practice Patterns at NCCN Institutions SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [McCormick, B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ottesen, R.; Mortimer, J.; Niland, J.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Hughes, M.; Weeks, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Javid, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Khan, S.] Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Edge, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S42 EP S43 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900110 ER PT J AU McCormick, B Moughan, J Hudis, C Kuerer, H Rakovitch, E Smith, B Sneige, N Shah, A Germain, I White, J AF McCormick, B. Moughan, J. Hudis, C. Kuerer, H. Rakovitch, E. Smith, B. Sneige, N. Shah, A. Germain, I. White, J. TI Low-risk Breast Ductal Carcinoma In Situ (DCIS): Results From the Radiation Therapy Oncology Group 9804 Phase 3 Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [McCormick, B.; Hudis, C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Moughan, J.] RTOG Stat Ctr, Philadelphia, PA USA. [Kuerer, H.; Sneige, N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Rakovitch, E.] Toronto Sunnybrook Reg Canc Ctr, Toronto, ON, Canada. [Smith, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shah, A.] York Canc Ctr, York, PA USA. [Germain, I.] Hotel Dieu Quebec, Quebec City, PQ, Canada. [White, J.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S5 EP S5 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900015 ER PT J AU Michaelson, E Chen, Y Silver, B Tishler, RB Marcus, KC Ng, AK Mauch, PM AF Michaelson, E. Chen, Y. Silver, B. Tishler, R. B. Marcus, K. C. Ng, A. K. Mauch, P. M. TI Thyroid Malignancies in Survivors of Hodgkin Lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Michaelson, E.; Chen, Y.; Silver, B.; Tishler, R. B.; Marcus, K. C.; Ng, A. K.; Mauch, P. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S614 EP S614 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902051 ER PT J AU Min, C Yock, T Winey, B MacDonald, SM Tarbell, NJ Adams, J Paganetti, H AF Min, C. Yock, T. Winey, B. MacDonald, S. M. Tarbell, N. J. Adams, J. Paganetti, H. TI Dose Response Relationship for Permanent Alopecia in Pediatric Medulloblastoma Patients Treated With Proton Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Min, C.; Yock, T.; Winey, B.; MacDonald, S. M.; Tarbell, N. J.; Adams, J.; Paganetti, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Min, C.; Winey, B.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S78 EP S78 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900194 ER PT J AU Min, C Zhu, X Winey, B Grogg, K Fakhri, GE Bortfeld, T Paganetti, H Shih, HA AF Min, C. Zhu, X. Winey, B. Grogg, K. Fakhri, G. E. Bortfeld, T. Paganetti, H. Shih, H. A. TI In Vivo Treatment Verification Using In-room PET in Proton Radiation Therapy: First Clinical Trials and Evaluation of Short-length Scan SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S53 EP S54 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900135 ER PT J AU Mirabeau-Beale, KL Chen, M Sun, L D'Amico, AV AF Mirabeau-Beale, K. L. Chen, M. Sun, L. D'Amico, A. V. TI Metachronous Cancer Diagnosis in Men With Prostate Cancer and the Risk of Prostate Cancer-specific Mortality: A Competing Risks Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mirabeau-Beale, K. L.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, M.] Univ Connecticut, Storrs, CT USA. [Sun, L.] NCI, DCCPS, Bethesda, MD 20892 USA. [D'Amico, A. V.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [D'Amico, A. V.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S540 EP S540 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901569 ER PT J AU Mohan, R Matney, JE Bluett, J Palmer, M Choi, N Chang, J Komaki, R Cox, J Liao, Z AF Mohan, R. Matney, J. E. Bluett, J. Palmer, M. Choi, N. Chang, J. Komaki, R. Cox, J. Liao, Z. TI IMRT Versus Passively Scattered Proton Therapy (PSPT) for Locally Advanced NSCLC - Impact of Changing Techniques and Technologies Over the Course of a Randomized Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Mohan, R.; Matney, J. E.; Bluett, J.; Palmer, M.; Chang, J.; Komaki, R.; Cox, J.; Liao, Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Choi, N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S565 EP S566 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901634 ER PT J AU Moore, KL Trofimov, AV Lu, H Efstathiou, J Appenzoller, LM Mutic, S AF Moore, K. L. Trofimov, A. V. Lu, H. Efstathiou, J. Appenzoller, L. M. Mutic, S. TI Interinstitutional Quality Control of IMRT Treatment Planning SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Moore, K. L.; Appenzoller, L. M.; Mutic, S.] Washington Univ, Sch Med, St Louis, MO USA. [Trofimov, A. V.; Lu, H.; Efstathiou, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S157 EP S157 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900389 ER PT J AU Ng, S Damato, AL Tishler, RB Cormack, RA AF Ng, S. Damato, A. L. Tishler, R. B. Cormack, R. A. TI Does 120 MLC-A Give an Advantage Over 120 MLC-B in the Treatment of Head-and-Neck Cancer (HNC) Patients? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Faber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S805 EP S806 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902557 ER PT J AU Ngwa, W Korideck, H Kimmelman, A Kassis, AI Kumar, R Sridhar, S Makrigiorgos, M Cormack, RA AF Ngwa, W. Korideck, H. Kimmelman, A. Kassis, A. I. Kumar, R. Sridhar, S. Makrigiorgos, M. Cormack, R. A. TI In Vitro Dose Enhancement From Gold Nanoparticles During Low-dose-rate Gamma Irradiation With I-125 Brachytherapy Seeds SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Ngwa, W.; Makrigiorgos, M.; Cormack, R. A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ngwa, W.; Korideck, H.; Kimmelman, A.; Kassis, A. I.; Makrigiorgos, M.; Cormack, R. A.] Harvard Univ, Sch Med, Boston, MA USA. [Kumar, R.; Sridhar, S.] Northeastern Univ, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S134 EP S134 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900333 ER PT J AU Paganetti, H Schuemann, J Grassberger, C Verburg, J Giantsoudi, D Moteabbed, M Min, C Testa, M Faddegon, B Perl, J AF Paganetti, H. Schuemann, J. Grassberger, C. Verburg, J. Giantsoudi, D. Moteabbed, M. Min, C. Testa, M. Faddegon, B. Perl, J. TI Advanced Dose Calculation to Reduce Uncertainties in Treatment Planning and Delivery for Proton Therapy Patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Paganetti, H.; Schuemann, J.; Grassberger, C.; Verburg, J.; Giantsoudi, D.; Moteabbed, M.; Min, C.; Testa, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Faddegon, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S55 EP S56 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900140 ER PT J AU Paly, JJ Hallemeier, CL Biggs, PJ Niemierko, A Roeder, F Martinez-Monge, R Whitson, JM Calvo, FA Fastner, G Efstathiou, JA AF Paly, J. J. Hallemeier, C. L. Biggs, P. J. Niemierko, A. Roeder, F. Martinez-Monge, R. Whitson, J. M. Calvo, F. A. Fastner, G. Efstathiou, J. A. TI Outcomes for a Multi-institutional Cohort of Patients Treated With Intraoperative Radiation Therapy for Advanced or Recurrent Renal Cell Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Paly, J. J.; Biggs, P. J.; Niemierko, A.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hallemeier, C. L.] Mayo Clin, Rochester, MN USA. [Roeder, F.] Univ Heidelberg, Heidelberg, Germany. [Martinez-Monge, R.] Univ Navarra, Pamplona, Spain. [Whitson, J. M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Calvo, F. A.] Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Fastner, G.] Univ Clin Radiotherapy & Radiooncol, Salzburg, Austria. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S424 EP S425 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901264 ER PT J AU Parekh, A Chen, M Dosoretz, DE Ross, R Salenius, S Graham, PL D'Amico, AV Nguyen, PL AF Parekh, A. Chen, M. Dosoretz, D. E. Ross, R. Salenius, S. Graham, P. L. D'Amico, A. V. Nguyen, P. L. TI Identification of Comorbidities That Place Men at Highest Risk of Harm From Androgen Deprivation Therapy for Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Parekh, A.; Graham, P. L.; D'Amico, A. V.; Nguyen, P. L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Parekh, A.; Graham, P. L.; D'Amico, A. V.; Nguyen, P. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Chen, M.] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Dosoretz, D. E.; Ross, R.; Salenius, S.] 21st Century Oncol, Ft Myers, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S93 EP S93 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900231 ER PT J AU Pashtan, IM Pan, E Chapman, PH Rowell, A Niemierko, A Bussiere, MR Oh, K Loeffler, JS Shih, HA AF Pashtan, I. M. Pan, E. Chapman, P. H. Rowell, A. Niemierko, A. Bussiere, M. R. Oh, K. Loeffler, J. S. Shih, H. A. TI Proton Radiosurgery for Management of Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Pashtan, I. M.] Harvard Radiat Oncol Program, Boston, MA USA. [Pan, E.; Chapman, P. H.; Rowell, A.; Niemierko, A.; Bussiere, M. R.; Oh, K.; Loeffler, J. S.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S291 EP S291 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900736 ER PT J AU Rao, SS Saleh, Z Tam, M Apte, A Sharp, G Setton, J Nancy, LY Deasy, JO AF Rao, S. S. Saleh, Z. Tam, M. Apte, A. Sharp, G. Setton, J. Nancy, L. Y. Deasy, J. O. TI A Novel Voxel-based Analysis of the Development of Trismus Following Chemoradiation for Oropharyngeal (OPC) Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Rao, S. S.; Saleh, Z.; Tam, M.; Apte, A.; Setton, J.; Nancy, L. Y.; Deasy, J. O.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Sharp, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S30 EP S31 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900078 ER PT J AU Roberge, D Bosch, W Bahig, H Levin, W Petersen, I Haddock, M Freeman, C DeLaney, T Abrams, R Wang, D AF Roberge, D. Bosch, W. Bahig, H. Levin, W. Petersen, I. Haddock, M. Freeman, C. DeLaney, T. Abrams, R. Wang, D. TI Interobserver Variation in Suspicious Edema Definition for Preoperative Radiation Therapy in Soft-tissue Sarcoma of the Extremity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Roberge, D.; Bahig, H.] CHUM Notre Dame, Montreal, PQ, Canada. [Roberge, D.; Freeman, C.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Bosch, W.] Washington Univ, St Louis, MO USA. [Levin, W.] Univ Penn, Philadelphia, PA 19104 USA. [Petersen, I.; Haddock, M.] Mayo Clin, Rochester, MN USA. [DeLaney, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Abrams, R.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Wang, D.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S168 EP S169 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900420 ER PT J AU Rochet, N Russell, AH Jee, KK Bortfeld, TR Craft, DL AF Rochet, N. Russell, A. H. Jee, K. K. Bortfeld, T. R. Craft, D. L. TI Multicriteria Optimization in Intensity Modulated Radiation Therapy Treatment Planning for Large Target Volumes: First Experience With Whole Abdomen Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Rochet, N.; Russell, A. H.; Jee, K. K.; Bortfeld, T. R.; Craft, D. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Rochet, N.] Univ Heidelberg, Dept Radiat Oncol, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S768 EP S768 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902459 ER PT J AU Rochet, N Kahn, RS Niemierko, A Delaney, TF Russell, AH AF Rochet, N. Kahn, R. S. Niemierko, A. Delaney, T. F. Russell, A. H. TI Consolidative Whole Abdomen Radiation Therapy After Surgery and Carboplatin-Taxol-based Chemotherapy for Advanced Epithelial Uterine Endometrial Malignancy: Feasibility and Clinical Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Rochet, N.; Niemierko, A.; Delaney, T. F.; Russell, A. H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Rochet, N.] Univ Heidelberg, Dept Radiat Oncol, Heidelberg, Germany. [Kahn, R. S.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S451 EP S451 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901332 ER PT J AU Rottmann, J Yue, Y Chen, A Kozono, D Mak, R Hacker, F Berbeco, RI AF Rottmann, J. Yue, Y. Chen, A. Kozono, D. Mak, R. Hacker, F. Berbeco, R. I. TI Real-time Tracking of Markerless Lung Tumors During SBRT With Continuous MV Imaging SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Rottmann, J.; Yue, Y.; Chen, A.; Kozono, D.; Mak, R.; Hacker, F.; Berbeco, R. I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rottmann, J.; Yue, Y.; Chen, A.; Kozono, D.; Mak, R.; Hacker, F.; Berbeco, R. I.] Harvard Univ, Sch Med, Boston, MA USA. [Rottmann, J.] German Canc Res Ctr, D-6900 Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S200 EP S200 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900500 ER PT J AU Sadek, BT Shenouda, MN Raad, RFA Niemierko, A Goldberg, SI Taghian, AG AF Sadek, B. T. Shenouda, M. N. Raad, R. F. Abi Niemierko, A. Goldberg, S. I. Taghian, A. G. TI Does Lobular Carcinoma In Situ (LCIS) at the Surgical Margins Increase the Risk of Local Failure in Patients With Invasive Breast Cancer Receiving Conservative Treatment? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Sadek, B. T.; Shenouda, M. N.; Raad, R. F. Abi; Niemierko, A.; Goldberg, S. I.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S187 EP S187 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900465 ER PT J AU Schoenfeld, JD Dyer, MA Alexander, BM Oh, KS Mahadevan, A Hodi, FS Sullivan, R McDermott, DF Kaplan, ID AF Schoenfeld, J. D. Dyer, M. A. Alexander, B. M. Oh, K. S. Mahadevan, A. Hodi, F. S. Sullivan, R. McDermott, D. F. Kaplan, I. D. TI Melanoma Brain Metastases Treated With Brain-directed Radiation Followed by Ipilimumab SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Schoenfeld, J. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Dyer, M. A.] Harvard Univ, Sch Med, Boston, MA USA. [Alexander, B. M.; Hodi, F. S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Alexander, B. M.; Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oh, K. S.; Sullivan, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mahadevan, A.; McDermott, D. F.; Kaplan, I. D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S287 EP S287 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900725 ER PT J AU Schoenfeld, JD Margalit, DN Kasperzyk, JL Shui, IM Rider, JR Epstein, MM Meisner, A Giovannucci, EL Stampfer, MJ Mucci, LA AF Schoenfeld, J. D. Margalit, D. N. Kasperzyk, J. L. Shui, I. M. Rider, J. R. Epstein, M. M. Meisner, A. Giovannucci, E. L. Stampfer, M. J. Mucci, L. A. TI Single Nucleotide Polymorphism in Inflammatory Gene RNASEL Predicts Outcome After Radiation Therapy for Localized Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Schoenfeld, J. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Margalit, D. N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Margalit, D. N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kasperzyk, J. L.; Shui, I. M.; Rider, J. R.; Epstein, M. M.; Meisner, A.; Giovannucci, E. L.; Stampfer, M. J.; Mucci, L. A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S57 EP S58 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900145 ER PT J AU Seco, J Harb, N Chen, W Simeone, F Yock, TI Kooy, H Delaney, T MacDonald, S AF Seco, J. Harb, N. Chen, W. Simeone, F. Yock, T. I. Kooy, H. Delaney, T. MacDonald, S. TI Decreased Vertebral Column Dose in Spinal Irradiation With IMPT and Proton Arc Techniques: Potential for Protons to Allow for CSI Without Inducing Spinal Growth Impairment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S834 EP S835 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902632 ER PT J AU Seco, J Reza, H Oh, K Doppke, K Spadea, M AF Seco, J. Reza, H. Oh, K. Doppke, K. Spadea, M. TI Stereotactic Body Radiation Therapy (SBRT) of Spine Lesions: Optimizing Number of IMRT Beams and Monte Carlo Assessment of Dose Predictions SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Seco, J.; Reza, H.; Oh, K.; Doppke, K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Seco, J.; Reza, H.; Oh, K.; Doppke, K.] Harvard Univ, Sch Med, Boston, MA USA. [Spadea, M.] Magna Graecia Univ Catanzaro, Catanzaro, Italy. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S820 EP S820 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902596 ER PT J AU Shah, A Paly, JJ Efstathiou, JA Bekelman, JE AF Shah, A. Paly, J. J. Efstathiou, J. A. Bekelman, J. E. TI Physician Evaluation of Web-based Consumer Health Information on Proton Therapy for Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Shah, A.; Bekelman, J. E.] Univ Penn, Philadelphia, PA 19104 USA. [Paly, J. J.; Efstathiou, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S98 EP S98 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900244 ER PT J AU Shenouda, M Sadek, BT Raad, RFA Goldberg, SI Taghian, AG AF Shenouda, M. Sadek, B. T. Raad, R. F. Abi Goldberg, S. I. Taghian, A. G. TI Prognostic Outcomes of Local-regional Recurrence in Breast Cancer Patients Treated by Breast-conservation Treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Shenouda, M.; Sadek, B. T.; Raad, R. F. Abi; Goldberg, S. I.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S36 EP S37 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900093 ER PT J AU Shih, HA Sherman, JC Nachtigall, LB Winrich, BK Yeap, BY Batchelor, TT Thornton, LT Oh, KS Curry, WT Loeffler, JS AF Shih, H. A. Sherman, J. C. Nachtigall, L. B. Winrich, B. K. Yeap, B. Y. Batchelor, T. T. Thornton, L. T. Oh, K. S. Curry, W. T. Loeffler, J. S. TI Proton Therapy for Low-grade Gliomas: A Pilot Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Shih, H. A.; Sherman, J. C.; Nachtigall, L. B.; Winrich, B. K.; Yeap, B. Y.; Batchelor, T. T.; Thornton, L. T.; Oh, K. S.; Curry, W. T.; Loeffler, J. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S37 EP S37 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900095 ER PT J AU Shusharina, N Chan, AW Adams, J Chen, GT Sharp, GC AF Shusharina, N. Chan, A. W. Adams, J. Chen, G. T. Sharp, G. C. TI Adaptive Proton Radiation Therapy for Base of Skull Tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Shusharina, N.; Chan, A. W.; Adams, J.; Chen, G. T.; Sharp, G. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S803 EP S803 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902550 ER PT J AU Shusharina, N Choi, NC Sharp, GC AF Shusharina, N. Choi, N. C. Sharp, G. C. TI Correlation of FDG Avid Volumes of Initial and Recurrent Lung Cancers After Radiation Therapy or Chemoradiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Shusharina, N.; Choi, N. C.; Sharp, G. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S104 EP S105 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900259 ER PT J AU Skolny, M Niemierko, A Miller, CL Shenouda, M Jammallo, LS Sadek, B O'Toole, J Specht, MC Taghian, AG AF Skolny, M. Niemierko, A. Miller, C. L. Shenouda, M. Jammallo, L. S. Sadek, B. O'Toole, J. Specht, M. C. Taghian, A. G. TI A Nomogram for Estimating the Risk of Lymphedema Following Treatment for Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Skolny, M.; Niemierko, A.; Miller, C. L.; Shenouda, M.; Jammallo, L. S.; Sadek, B.; O'Toole, J.; Specht, M. C.; Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S115 EP S115 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900287 ER PT J AU Spadea, M Fassi, A Depauw, N Riboldi, M Baroni, G Seco, J AF Spadea, M. Fassi, A. Depauw, N. Riboldi, M. Baroni, G. Seco, J. TI Contrast Enhanced Proton Radiography for In-room Soft Tissue-based Setup SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Spadea, M.] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Fassi, A.; Riboldi, M.; Baroni, G.] Politecn Milan Univ, Milan, Italy. [Depauw, N.] Univ Wollongong, CMRP, Wollongong, NSW, Australia. [Seco, J.] Harvard Univ, Sch Med, Boston, MA USA. [Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S53 EP S53 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900134 ER PT J AU Sperduto, PW Shanley, R Kased, N Roberge, D Chao, ST Jensen, AW Shih, HA Kirkpatrick, J Gaspar, LE Mehta, M AF Sperduto, P. W. Shanley, R. Kased, N. Roberge, D. Chao, S. T. Jensen, A. W. Shih, H. A. Kirkpatrick, J. Gaspar, L. E. Mehta, M. TI The Effect of Tumor Subtype on the Time From Primary Diagnosis to Development of Brain Metastases and Survival in Women With Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Sperduto, P. W.] Univ Minnesota, Gamma Knife Ctr, Minneapolis, MN USA. [Shanley, R.] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Kased, N.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Roberge, D.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Chao, S. T.] Cleveland Clin, Cleveland, OH 44106 USA. [Jensen, A. W.] Mayo Clin, Rochester, MN USA. [Jensen, A. W.] Sanford Roger Maria Canc Ctr, Fargo, ND USA. [Shih, H. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kirkpatrick, J.] Duke Univ, Med Ctr, Durham, NC USA. [Gaspar, L. E.] Univ Colorado, Sch Med, Aurora, CO USA. [Mehta, M.] Northwestern Univ, Chicago, IL 60611 USA. [Mehta, M.] Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S142 EP S142 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900353 ER PT J AU Taghian, AG Ancukiewicz, M Smith, B MacDonald, S Specht, M Levy, A Hirsch, A Kachnic, L Powell, S Recht, A AF Taghian, A. G. Ancukiewicz, M. Smith, B. MacDonald, S. Specht, M. Levy, A. Hirsch, A. Kachnic, L. Powell, S. Recht, A. TI Three-Dimensional Conformal External Beam Accelerated Partial Breast Irradiation (3D-APBI): Results of a Phase I Dose Escalation Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Taghian, A. G.; Ancukiewicz, M.; Smith, B.; MacDonald, S.; Specht, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Levy, A.] Inst Gustave Roussy, Paris, France. [Hirsch, A.; Kachnic, L.] Boston Med Ctr, Boston, MA USA. [Powell, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Recht, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S86 EP S87 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900215 ER PT J AU Townamchai, K Lee, LJ Poorvu, PD Viswanathan, AN AF Townamchai, K. Lee, L. J. Poorvu, P. D. Viswanathan, A. N. TI Clinical Outcomes With Dose Escalation Using Intensity Modulated Radiation Therapy for Node-Positive Endometrial and Cervical Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Townamchai, K.; Lee, L. J.; Poorvu, P. D.; Viswanathan, A. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S454 EP S454 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901340 ER PT J AU Truong, P Alexander, C Sadek, B Shenouda, M Raad, RA Olivotto, I Taghian, A AF Truong, P. Alexander, C. Sadek, B. Shenouda, M. Raad, R. Abi Olivotto, I. Taghian, A. TI Is Triple Negative Subtype Associated With Higher Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Truong, P.; Alexander, C.; Olivotto, I.] BC Canc Agcy, Victoria, BC, Canada. [Sadek, B.; Shenouda, M.; Raad, R. Abi; Taghian, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Sadek, Betro/I-7734-2013 OI Sadek, Betro/0000-0003-0119-7207 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S140 EP S140 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900348 ER PT J AU Tseng, YD Wo, JY Ancukiewicz, M Adams, J Panahandeh, H Depauw, N Hong, TS AF Tseng, Y. D. Wo, J. Y. Ancukiewicz, M. Adams, J. Panahandeh, H. Depauw, N. Hong, T. S. TI Dosimetric and Clinical Predictors of Nausea and Vomiting: An Exploratory Analysis of a Prospective Phase I/II Trial With Neoadjuvant Accelerated Short Course Radiation Therapy With Capecitabine for Resectable Pancreatic Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Tseng, Y. D.] Harvard Radiat Oncol Program, Boston, MA USA. [Wo, J. Y.; Ancukiewicz, M.; Adams, J.; Panahandeh, H.; Depauw, N.; Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S321 EP S322 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900817 ER PT J AU Vichare, AM Eads, N Punglia, R Potters, L AF Vichare, A. M. Eads, N. Punglia, R. Potters, L. TI Performance Assessment for the Advancement of Radiation Oncology Treatment (PAAROT): A Practical Approach for Informing Practice Improvement SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Vichare, A. M.; Eads, N.] ASTRO, Fairfax, VA USA. [Punglia, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Potters, L.] N Shore LIJ Hlth Syst, New Hyde Pk, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S533 EP S534 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901554 ER PT J AU Wang, Y Schneider, RJ Crawford, BT Chen, H Trofimov, AV Gierga, DP Efstathiou, JA Zietman, AL Lu, H AF Wang, Y. Schneider, R. J. Crawford, B. T. Chen, H. Trofimov, A. V. Gierga, D. P. Efstathiou, J. A. Zietman, A. L. Lu, H. TI Comparison of Imaging Dose From Daily Cone Beam CT to Out-of-Field Therapeutic Dose in IMRT and VMAT Treatments of Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Wang, Y.; Schneider, R. J.; Crawford, B. T.; Chen, H.; Trofimov, A. V.; Gierga, D. P.; Efstathiou, J. A.; Zietman, A. L.; Lu, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S762 EP S763 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902444 ER PT J AU Willers, H Birkelbach, M Ferraiolo, N Gheorghiu, L Pfaeffle, H Daly, B Dahm-Daphi, J Benes, C Zou, L Kachnic, L AF Willers, H. Birkelbach, M. Ferraiolo, N. Gheorghiu, L. Pfaeffle, H. Daly, B. Dahm-Daphi, J. Benes, C. Zou, L. Kachnic, L. TI Recombinational DNA Repair Defects in Lung Cancer and PARP Inhibitor Sensitivity SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Willers, H.; Ferraiolo, N.; Gheorghiu, L.; Pfaeffle, H.; Benes, C.; Zou, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Birkelbach, M.; Dahm-Daphi, J.] Univ Hamburg, Hamburg, Germany. [Daly, B.; Kachnic, L.] Boston Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S126 EP S127 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542900315 ER PT J AU Wo, JY Mamon, HJ Ferrone, CR Ryan, DP Blaszkowsky, LS Kwak, EL Swanson, RS Lillemoe, KD Fernandez-Del Castillo, C Hong, TS AF Wo, J. Y. Mamon, H. J. Ferrone, C. R. Ryan, D. P. Blaszkowsky, L. S. Kwak, E. L. Swanson, R. S. Lillemoe, K. D. Fernandez-Del Castillo, C. Hong, T. S. TI Phase I Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Wo, J. Y.; Ferrone, C. R.; Ryan, D. P.; Blaszkowsky, L. S.; Kwak, E. L.; Lillemoe, K. D.; Fernandez-Del Castillo, C.; Hong, T. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mamon, H. J.; Swanson, R. S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S336 EP S336 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542901031 ER PT J AU Xiang, HF Lu, H Hirsch, AE Efstathiou, JA Zietman, AL Harris, K Bloch, N Keohan, S Willins, J Kachnic, LA AF Xiang, H. F. Lu, H. Hirsch, A. E. Efstathiou, J. A. Zietman, A. L. Harris, K. Bloch, N. Keohan, S. Willins, J. Kachnic, L. A. TI Endorectal Balloon in Stereotactic Body Radiation Therapy (SBRT) for Early-Stage Prostate Cancer: A Planning and Dosimetry Analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Xiang, H. F.; Lu, H.; Hirsch, A. E.; Efstathiou, J. A.; Zietman, A. L.; Willins, J.; Kachnic, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Xiang, H. F.; Lu, H.; Hirsch, A. E.; Efstathiou, J. A.; Zietman, A. L.; Willins, J.; Kachnic, L. A.] Harvard Univ, Sch Med, Boston, MA USA. [Xiang, H. F.; Hirsch, A. E.; Bloch, N.; Keohan, S.; Willins, J.; Kachnic, L. A.] Boston Med Ctr, Boston, MA USA. [Xiang, H. F.; Hirsch, A. E.; Bloch, N.; Keohan, S.; Willins, J.; Kachnic, L. A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Harris, K.] MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S832 EP S832 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902625 ER PT J AU Yue, Y Aristophanous, M Chen, AB Killoran, J Yap, J Berbeco, RI AF Yue, Y. Aristophanous, M. Chen, A. B. Killoran, J. Yap, J. Berbeco, R. I. TI A Novel Hybrid Multimodal Registration for Lung Radiation Therapy Response Evaluation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) C1 [Yue, Y.; Chen, A. B.; Killoran, J.; Yap, J.; Berbeco, R. I.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Aristophanous, M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2012 VL 84 IS 3 SU S BP S755 EP S756 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 030BP UT WOS:000310542902427 ER PT J AU Meyerhardt, JA Sato, K Niedzwiecki, D Ye, C Saltz, LB Mayer, RJ Mowat, RB Whittom, R Hantel, A Benson, A Wigler, DS Venook, A Fuchs, CS AF Meyerhardt, Jeffrey A. Sato, Kaori Niedzwiecki, Donna Ye, Cynthia Saltz, Leonard B. Mayer, Robert J. Mowat, Rex B. Whittom, Renaud Hantel, Alexander Benson, Al Wigler, Devin S. Venook, Alan Fuchs, Charles S. TI Dietary Glycemic Load and Cancer Recurrence and Survival in Patients with Stage III Colon Cancer: Findings From CALGB 89803 SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BODY-MASS INDEX; FOOD-FREQUENCY QUESTIONNAIRE; GROWTH-FACTOR-I; CORONARY-HEART-DISEASE; TOTAL-ENERGY-INTAKE; PLASMA C-PEPTIDE; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; CARBOHYDRATE INTAKE; WOMENS HEALTH AB Background The influence of glycemic load and related measures on survival among colon cancer patients remains largely unknown. Methods We conducted a prospective, observational study of 1011 stage III colon cancer patients reporting dietary intake during and 6 months after participation in an adjuvant chemotherapy trial. We examined the influence of glycemic load, glycemic index, fructose, and carbohydrate intakes on cancer recurrence and mortality using Cox proportional hazards regression; all tests of statistical significance were two-sided. Results Stage III colon cancer patients in the highest quintile of dietary glycemic load experienced an adjusted hazard ratio (HR) for disease-free survival of 1.79 (95% confidence interval [CI] 1.29 to 2.48), compared with those in the lowest quintile (P-trend across quintiles <.001). Increased glycemic load was associated with similar detriments in recurrence-free (P-trend across quintiles <.001) and overall survival (P-trend across quintiles <.001). These associations differed statistically significant by body mass index (BMI) (P-interaction .01). Whereas glycemic load was not associated with disease-free survival in patients with BMI < 25kg/m(2), higher glycemic load was statistically significant associated with worse disease-free survival among overweight or obese participants (BMI epsilon 25kg/m(2); HR 2.26; 95% CI 1.53 to 3.32; P-trend across quintiles <.001). Increasing total carbohydrate intake was similarly associated with inferior disease-free, recurrence-free, and overall survival (P-trend across quintiles <.001). Conclusion Higher dietary glycemic load and total carbohydrate intake were statistically significant associated with an increased risk of recurrence and mortality in stage III colon cancer patients. These findings support the role of energy balance factors in colon cancer progression and may offer potential opportunities to improve patient survival. C1 [Meyerhardt, Jeffrey A.; Sato, Kaori; Mayer, Robert J.; Wigler, Devin S.; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Niedzwiecki, Donna; Ye, Cynthia] Duke Univ, Med Ctr, Canc & Leukemia Grp Stat Ctr B, Durham, NC USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mowat, Rex B.] Toledo Community Hosp, Oncol Program, Toledo, OH USA. [Whittom, Renaud] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Hantel, Alexander] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Benson, Al] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. [Venook, Alan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jmeyerhardt@partners.org OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute [CA31946, CA33601, CA 118553, CA149222]; Pfizer Oncology; GI SPORE grant [P50CA127003]; [CA71323]; [CA29165]; [CA45418]; [CA32291]; [CA04326]; [CA47577]; [CA77597]; [CA45389]; [CA35279]; [CA77651]; [CA114558-02]; [CA45564]; [CA04457]; [CA35421]; [CA08025]; [CA59518]; [CA45808]; [CA21060]; [CA77658]; [CA11789]; [CA60138]; [CA41287]; [CA74811]; [CA47642]; [CA31983]; [CA37135]; [CA16450]; [CA12046]; [CA77298]; [CA47559]; [CA47555]; [CA77406]; [CA03927]; [CA26806]; [CA77440]; [CA07968] FX National Cancer Institute (CA31946 to the Cancer and Leukemia Group B, Monica M. Bertagnolli, MD, chairman; CA33601 to the CALGB Statistical Center, Daniel J. Sargent, PhD; CA 118553 and CA149222 to JAM and CSF); Pharmacia & Upjohn Company, now Pfizer Oncology; GI SPORE grant (P50CA127003 to JAM and CSF).; The following institutions participated in this study: Baptist Cancer Institute CCOP, Memphis, TN, Lee S. Schwartzberg, MD, supported by CA71323; Cancer Centers of the Carolinas, Greenville, SC, Jeffrey K. Giguere, MD, supported by CA29165; Christiana Care Health Services, Inc CCOP, Wilmington, DE, Stephen Grubbs, MD, supported by CA45418; Dana-Farber Cancer Institute, Boston, MA, Harold J. Burstein, MD, PhD, supported by CA32291; Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH, Konstantin Dragnev, MD, supported by CA04326; Duke University Medical Center, Durham, NC, Jeffrey Crawford, MD, supported by CA47577; Georgetown University Medical Center, Washington, DC, Minetta C. Liu, MD, supported by CA77597; Hematology-Oncology Associates of Central New York CCOP, Syracuse, NY, Jeffrey Kirshner, MD, supported by CA45389; Long Island Jewish Medical Center, Lake Success, NY, Kanti R. Rai, MD, supported by CA35279; Massachusetts General Hospital, Boston, MA, Jeffrey W. Clark, MD, supported by CA32291; Memorial Sloan-Kettering Cancer Center, New York, NY, Clifford A. Hudis, MD, supported by CA77651; Missouri Baptist Medical Center, St. Louis, MO, Alan P. Lyss, MD, supported by CA114558-02; Mount Sinai Medical Center, Miami, FL, Michael A. Schwartz, MD, supported by CA45564; Mount Sinai School of Medicine, New York, NY, Lewis R. Silverman, MD, supported by CA04457; Nevada Cancer Research Foundation CCOP, Las Vegas, NV, John A. Ellerton, MD, supported by CA35421; North Shore-Long Island Jewish Health System, New Hyde Park, NY, Daniel Budman, MD, supported by CA35279; Rhode Island Hospital, Providence, RI, William Sikov, MD, supported by CA08025; Roswell Park Cancer Institute, Buffalo, NY, Ellis Levine, MD, supported by CA59518; Southeast Cancer Control Consortium Inc CCOP, Goldsboro, NC, James N. Atkins, MD, supported by CA45808; State University of New York Upstate Medical University, Syracuse, NY, Stephen L. Graziano, MD, supported by CA21060; The Ohio State University Medical Center, Columbus, OH, Clara D. Bloomfield, MD, supported by CA77658; University of California at San Diego, San Diego, CA, Barbara A. Parker, MD, supported by CA11789; University of California at San Francisco, San Francisco, CA, Charles J. Ryan, MD, supported by CA60138; University of Chicago, Chicago, IL, Hedy L. Kindler, MD, supported by CA41287; University of Illinois MBCCOP, Chicago, IL, David J. Peace, MD, supported by CA74811; University of Iowa, Iowa City, IA, Daniel A. Vaena, MD, supported by CA47642; University of Maryland Greenebaum Cancer Center, Baltimore, MD, Martin Edelman, MD, supported by CA31983; University of Massachusetts Medical School, Worcester, MA, William V. Walsh, MD, supported by CA37135; University of Minnesota, Minneapolis, MN, Bruce A Peterson, MD, supported by CA16450; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO, Carl E. Freter, MD, supported by CA12046; University of Nebraska Medical Center, Omaha, NE, Anne Kessinger, MD, supported by CA77298; University of North Carolina at Chapel Hill, Chapel Hill, NC, Thomas C. Shea, MD, supported by CA47559; University of Tennessee Memphis, Memphis, TN, Harvey B. Niell, MD, supported by CA47555; University of Vermont, Burlington, VT, Steven M. Grunberg, MD, supported by CA77406; Wake Forest University School of Medicine, Winston-Salem, NC, David D. Hurd, MD, supported by CA03927; Walter Reed Army Medical Center, Washington, DC, Brendan M. Weiss, MD, supported by CA26806; Washington University School of Medicine, St.; Louis, MO, Nancy Bartlett, MD, supported by CA77440; Weill Medical College of Cornell University, New York, NY, John Leonard, MD, supported by CA07968. NR 61 TC 43 Z9 43 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 22 BP 1702 EP 1711 DI 10.1093/jnci/djs399 PG 10 WC Oncology SC Oncology GA 045BK UT WOS:000311669100006 PM 23136358 ER PT J AU Maiellaro, I Lefkimmiatis, K Moyer, MP Curci, S Hofer, AM AF Maiellaro, Isabella Lefkimmiatis, Konstantinos Moyer, Mary Pat Curci, Silvana Hofer, Aldebaran M. TI Termination and activation of store-operated cyclic AMP production SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE calcium; cyclic AMP; endoplasmic reticulum ID INTERACTION MOLECULE-1 STIM1; ADENYLYL-CYCLASE ISOFORMS; ENDOPLASMIC-RETICULUM; INTRACELLULAR CA2+; CRAC CHANNEL; PLASMA-MEMBRANE; DEFICIENT MICE; CALCIUM-ENTRY; NCB-20 CELLS; CAMP AB Diverse pathophysiological processes (e.g. obesity, lifespan determination, addiction and male fertility) have been linked to the expression of specific isoforms of the adenylyl cyclases (AC1-AC10), the enzymes that generate cyclic AMP (cAMP). Our laboratory recently discovered a new mode of cAMP production, prominent in certain cell types, that is stimulated by any manoeuvre causing reduction of free [Ca2+] within the lumen of the endoplasmic reticulum (ER) calcium store. Activation of this store-operated pathway requires the ER Ca2+ sensor, STIM1, but the identity of the enzymes responsible for cAMP production and how this process is regulated is unknown. Here, we used sensitive FRET-based sensors for cAMP in single cells combined with silencing and overexpression approaches to show that store-operated cAMP production occurred preferentially via the isoform AC3 in NCM460 colonic epithelial cells. Ca2+ entry via the plasma membrane Ca2+ channel, Orai1, suppressed cAMP production, independent of store refilling. These findings are an important first step towards defining the functional significance and to identify the protein composition of this novel Ca2+/cAMP crosstalk system. C1 [Maiellaro, Isabella; Lefkimmiatis, Konstantinos; Curci, Silvana; Hofer, Aldebaran M.] Harvard Univ, VA Boston Healthcare Syst, Sch Med, Dept Surg,Brigham & Womens Hosp, W Roxbury, MA 02132 USA. [Moyer, Mary Pat] INCELL Corp LLC, San Antonio, TX USA. RP Hofer, AM (reprint author), Harvard Univ, VA Boston Healthcare Syst, Sch Med, 1400 VFW Pkwy,Room 2B111, W Roxbury, MA 02132 USA. EM ahofer@rics.bwh.harvard.edu RI Lefkimmiatis, Konstantinos/I-1239-2016 OI Lefkimmiatis, Konstantinos/0000-0001-7137-7866 FU Harvard Digestive Diseases Center [5P30DK034854-24]; NIDDK [1R21DK088197-01]; Medical Research Service of the Veteran's Administration [VA-ORD 1 I01 BX000968-01] FX We are thankful for the kind gift of plasmids from Dr. Kees Jalink, Netherlands Cancer Center (EpacH30), Dr. Roger Y. Tsien, UCSD (mCherry), Dr. Carole A. Parent, National Cancer Institute (AC3-GFP), Dr. Tobias Meyer, Stanford University (STIM1), Dr. Marie Dziadek, Garvan Institute, Australia (STIM2). Thanks are given to Jonathan M. Nichols and Christina N. Dragon for excellent technical assistance. We gratefully acknowledge support from the Harvard Digestive Diseases Center (5P30DK034854-24), the NIDDK (1R21DK088197-01) and the Medical Research Service of the Veteran's Administration (VA-ORD 1 I01 BX000968-01), all to AMH. NR 52 TC 5 Z9 5 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-1838 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD NOV PY 2012 VL 16 IS 11 BP 2715 EP 2725 DI 10.1111/j.1582-4934.2012.01592.x PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 030FM UT WOS:000310555200016 PM 22681560 ER PT J AU Wu, CC Cronin, CG Chu, JT Halpern, EF Sahani, DV Shepard, JAO Gilman, MD AF Wu, Carol C. Cronin, Carmel G. Chu, Julia T. Halpern, Elkan F. Sahani, Dushyant V. Shepard, Jo-Anne O. Gilman, Matthew D. TI Incidental Pulmonary Nodules Detected on Abdominal Computed Tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; pulmonary nodules; thoracic imaging ID LUNG-CANCER; CT AB Objectives: To review the characteristics and outcome of incidental pulmonary nodules reported on abdominal computed tomography (CT). Methods: A database search of abdominal CTs from January 1, 2004, to December 31, 2006, revealed 413 patients with incidental pulmonary nodules and at least one follow-up chest CT. Demographic information, nodule characteristics, and eventual outcome of the nodules were analyzed. Results: Of the 413 patients, 56% had benign nodules, 11% had malignant nodules, and the remaining 33% had insufficient follow-up. There was a statistically significant difference (P < 0.05) in the age of the patients, history of malignancy, and size of the incidental nodule between benign and malignant groups. No malignant nodules were found in patients younger than 59 years who did not have a known or suspected malignancy. Conclusion: Small pulmonary nodules (<8 mm) on abdominal CT in patients younger than 50 years with no history of malignancy are unlikely to be malignant. C1 [Wu, Carol C.; Halpern, Elkan F.; Sahani, Dushyant V.; Shepard, Jo-Anne O.; Gilman, Matthew D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cronin, Carmel G.] Master Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. [Chu, Julia T.] Univ Calif Irvine, Dept Pathol & Lab Med, Med Ctr, Irvine, CA USA. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Radiol Thorac Imaging & Intervent, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM cwu8@partners.org NR 9 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2012 VL 36 IS 6 BP 641 EP 645 DI 10.1097/RCT.0b013e31826a0de2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 047HM UT WOS:000311830000003 PM 23192199 ER PT J AU Paczynski, M Kuperberg, GR AF Paczynski, Martin Kuperberg, Gina R. TI Multiple influences of semantic memory on sentence processing: Distinct effects of semantic relatedness on violations of real-world event/state knowledge and animacy selection restrictions SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article DE Animacy; ERP; P600; Real-world knowledge; Semantic; N400 ID EVENT-RELATED POTENTIALS; RIGHT CEREBRAL HEMISPHERES; LEXICAL DECISION TASK; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; SPREADING ACTIVATION; ELECTROPHYSIOLOGICAL EVIDENCE; THEMATIC RELATIONSHIPS; LIMITED-CAPACITY; LEVEL CONTEXT AB We aimed to determine whether semantic relatedness between an incoming word and its preceding context can override expectations based on two types of stored knowledge: real-world knowledge about the specific events and states conveyed by a verb, and the verb's broader selection restrictions on the animacy of its argument. We recorded event-related potentials on post-verbal Agent arguments as participants read and made plausibility judgments about passive English sentences. The N400 evoked by incoming animate Agent arguments that violated expectations based on real-world event/state knowledge, was strongly attenuated when they were semantically related to the context. In contrast, semantic relatedness did not modulate the N400 evoked by inanimate Agent arguments that violated the preceding verb's animacy selection restrictions. These findings suggest that, under these task and experimental conditions, semantic relatedness can facilitate processing of post-verbal animate arguments that violate specific expectations based on real-world event/state knowledge, but only when the semantic features of these arguments match the coarser-grained animacy restrictions of the verb. Animacy selection restriction violations also evoked a P600 effect, which was not modulated by semantic relatedness, suggesting that it was triggered by propositional impossibility. Together, these data indicate that the brain distinguishes between real-world event/state knowledge and animacy-based selection restrictions during online processing. Published by Elsevier Inc. C1 [Paczynski, Martin; Kuperberg, Gina R.] Tufts Univ, Dept Psychol, NeuroCognit Lab, Medford, MA 02155 USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Kuperberg, GR (reprint author), Tufts Univ, Dept Psychol, NeuroCognit Lab, 490 Boston Ave, Medford, MA 02155 USA. EM kuperber@nmr.mgh.harvard.edu FU NIMH [R01 MH071635]; NARSAD; Sidney Baer Trust FX This work was supported by NIMH (R01 MH071635) and NARSAD (with the Sidney Baer Trust). We thank Karin Blais, Tali Ditman-Brunye, Daya Gulabani and Donna Kreher for their help in developing experimental sentences and their assistance in running participants in the ERP portion of the study. We are also grateful for the thorough and thoughtful comments on previous version of the manuscript by Colin Phillips and Wing Yee Chow. NR 111 TC 36 Z9 38 U1 4 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD NOV PY 2012 VL 67 IS 4 BP 426 EP 448 DI 10.1016/j.jml.2012.07.003 PG 23 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA 046LW UT WOS:000311767500002 PM 23284226 ER PT J AU Costine, BA Quebeda-Clerkin, PB Dodge, CP Harris, BT Hillier, SC Duhaime, AC AF Costine, Beth A. Quebeda-Clerkin, Patricia B. Dodge, Carter P. Harris, Brent T. Hillier, Simon C. Duhaime, Ann-Christine TI Neuron-Specific Enolase, but Not S100B or Myelin Basic Protein, Increases in Peripheral Blood Corresponding to Lesion Volume after Cortical Impact in Piglets SO JOURNAL OF NEUROTRAUMA LA English DT Article DE age; biomarkers; controlled cortical impact ID TRAUMATIC BRAIN-INJURY; CEREBROSPINAL-FLUID; SERUM-LEVELS; CHILDREN; RAT; INFANTS; NEURODEGENERATION; MARKERS; SWINE AB A peripheral indicator of the presence and magnitude of brain injury has been a sought-after tool by clinicians. We measured neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, prior to and after scaled cortical impact in immature pigs, to determine if these purported markers increase after injury, correlate with the resulting lesion volume, and if these relationships vary with maturation. Scaled cortical impact resulted in increased lesion volume with increasing age. Concentrations of NSE, but not S100B or MBP, increased after injury in all age groups. The high variability of S100B concentrations prior to injury may have precluded detection of an increase due to injury. Total serum markers were estimated, accounting for the allometric growth of blood volume, and resulted in a positive correlation of both NSE and S100B with lesion volume. Even with allometric scaling of blood volume and a uniform mechanism of injury, NSE had only a fair to poor predictive value. In a clinical setting, where the types of injuries are varied, more investigation is required to yield a panel of serum markers that can reliably predict the extent of injury. Allometric scaling may improve estimation of serum marker release in pediatric populations. C1 [Costine, Beth A.; Duhaime, Ann-Christine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Quebeda-Clerkin, Patricia B.] Childrens Hosp Cent Calif, Dept Neurosurg, Madera, CA USA. [Dodge, Carter P.; Hillier, Simon C.] Dartmouth Hitchcock Med Ctr, Dept Anesthesiol, Dartmouth Med Sch, Lebanon, NH 03766 USA. [Harris, Brent T.] Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. [Harris, Brent T.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. RP Costine, BA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, 149 13th St,Room 3-405, Charlestown, MA 02129 USA. EM bcostine@partners.org FU NIH's National Institute of Child Health and Human Development [R01 (HD45364-5)]; Pediatric Neurosurgery Research Fund from the Children's Hospital at Dartmouth; Nicolas T. Zervas Endowed Chair Fund of Massachusetts General Hospital Department of Neurosurgery FX This study was supported by an R01 (HD45364-5) from the NIH's National Institute of Child Health and Human Development, the Pediatric Neurosurgery Research Fund from the Children's Hospital at Dartmouth, and the Nicolas T. Zervas Endowed Chair Fund of Massachusetts General Hospital Department of Neurosurgery. NR 35 TC 6 Z9 9 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV PY 2012 VL 29 IS 17 BP 2689 EP 2695 DI 10.1089/neu.2012.2428 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 047QU UT WOS:000311856400010 PM 22867012 ER PT J AU Saylor, PJ Mahmood, U Kunawudhi, A Smith, MR Palmer, EL Michaelson, MD AF Saylor, Philip J. Mahmood, Umar Kunawudhi, Anchisa Smith, Matthew R. Palmer, Edwin L. Michaelson, M. Dror TI Multitargeted Tyrosine Kinase Inhibition Produces Discordant Changes Between Tc-99m-MDP Bone Scans and Other Disease Biomarkers: Analysis of a Phase II Study of Sunitinib for Metastatic Castration-Resistant Prostate Cancer SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE bone scan; prostate cancer; tyrosine kinase inhibitor; sunitinib; bone metastases ID OPEN-LABEL; DOSE-ESCALATION; TRIAL; PREDNISONE; DOCETAXEL; MITOXANTRONE; GEFITINIB; MEN; LOCALIZATION; SURVIVAL AB One of the central unanswered questions in prostate cancer research is the significance of tyrosine kinase inhibitor (TKI) induced improvements in Tc-99m-methylene diphosphonate (Tc-99m-MDP) bone scans. Multitargeted tyrosine kinase inhibition has recently shown promise in the management of castration-resistant prostate cancer. In some cases, TKI inhibition has produced unprecedented improvements in bone metastases as detected by Tc-99m-MDP bone scans. The significance of these improvements is not known. In order to gain insight about the effects of TKIs on bone scans in prostate cancer, we systematically evaluated images from a phase II study of sunitinib, a multitargeted TKI. Methods: We analyzed images and data from a previously reported open-label phase II study that enrolled 34 men with advanced castration-resistant prostate cancer. Participants received sunitinib in 6-wk cycles (50 mg daily; 4 wk on, 2 wk off). We examined baseline and 12-wk bone scan images. Partial response was defined as an improvement of at least 50% in previous metastatic lesions subjectively or a change from prior diffuse skeletal metastases (superscan) to recognizable individual metastatic lesions. Our primary objective was to define the incidence of at least partial bone scan response. We also examined concomitant changes in CT and prostate-specific antigen (PSA) evidence of disease. Results: Analysis at 12 wk revealed 1 partial response by the response evaluation criteria in solid tumors (RECIST) and 2 confirmed PSA responses. There were 25 subjects who underwent bone scans at both time points (baseline and week 12) and who had bone metastases detectable at baseline. Within that group of 25, we found 5 bone scan partial responses and 1 complete response. None of those 6 subjects exhibited a PSA response (>= 50% decline from baseline) or RECIST response. Conclusion: We found a relatively high rate of Tc-99m-MDP bone scan response to sunitinib among men with metastatic prostate cancer. Further, we found that none of the subjects exhibiting bone scan responses experienced concordant improvements in PSA or CT evidence of disease by accepted criteria. This discordance argues that osteoblastic assessment provides an incomplete assessment of treatment-induced changes. Rational development of multitargeted TKIs for prostate cancer requires improved understanding of treatment-induced bone scan changes. Optimal imaging strategies may include evaluation of perfusion or direct tumor activity. C1 [Mahmood, Umar; Kunawudhi, Anchisa; Palmer, Edwin L.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. [Saylor, Philip J.; Smith, Matthew R.; Michaelson, M. Dror] Massachusetts Gen Hosp MGH, Ctr Canc, Div Hematol Oncol, Boston, MA USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. OI Michaelson, Dror/0000-0001-9249-6338 FU Dana-Farber/Harvard Cancer Center SPORE in Prostate Cancer; Prostate Cancer Foundation; National Institutes of Health [5K24CA121990-02]; Department of Defense (DOD) office of Congressionally Directed Medical Research Programs (CDMRP) FX This study was supported by grants from the Dana-Farber/Harvard Cancer Center SPORE in Prostate Cancer, the Prostate Cancer Foundation, and the National Institutes of Health (5K24CA121990-02). The clinical trial (Clinicaltrials.gov identifier: NCT00299741) was funded by a grant from the Department of Defense (DOD) office of Congressionally Directed Medical Research Programs (CDMRP). No other potential conflict of interest relevant to this article was reported. NR 28 TC 12 Z9 13 U1 0 U2 5 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2012 VL 53 IS 11 BP 1670 EP 1675 DI 10.2967/jnumed.112.105007 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037TC UT WOS:000311128400009 PM 22984218 ER PT J AU Singhal, T Narayanan, TK Jacobs, MP Bal, C Mantil, JC AF Singhal, Tarun Narayanan, Tanjore K. Jacobs, Martin P. Bal, Chandrashekhar Mantil, Joseph C. TI C-11-Methionine PET for Grading and Prognostication in Gliomas: A Comparison Study with F-18-FDG PET and Contrast Enhancement on MRI SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE gliomas; positron emission tomography; methionine; fluorodeoxyglucose; MRI ID POSITRON-EMISSION-TOMOGRAPHY; PRIMARY BRAIN-TUMORS; CEREBRAL GLIOMAS; C-11 METHIONINE; SURVIVAL; FLUORODEOXYGLUCOSE; DIFFERENTIATION; MANAGEMENT; CANCER AB The aim of this study was to compare the grading and prognostic value of L-[methyl-C-11]-methionine (C-11-MET) PET in glioma patients with F-18-FDG PET and contrast-enhanced MRI. Methods: Patients (n = 102) with histopathologically confirmed gliomas were followed up for an average of 34.6 +/- 3.8 mo after PET. The median survival was 18 +/- 4.7 mo in the high-grade glioma group and 58 +/- 27 mo in the low-grade glioma group. Patients underwent F-18-FDG PET, C-11-MET PET, and MRI in the diagnostic and preoperative stage. The ratio of the mean standardized uptake value in the tumor to mean standardized uptake value in contralateral normal cortex (T/N ratio) was calculated. Kaplan-Meier survival analysis and ANOVA were performed. Results: T/N ratios for C-11-MET PET and F-18-FDG PET were significantly higher in high-grade gliomas than in low-grade gliomas (2.15 +/- 0.77 vs. 1.56 +/- 0.74, P < 0.001, and 0.85 +/- 0.61 vs. 0.63 +/- 0.37, P < 0.01, respectively). Median survival was 19 5.4 mo in patients with a TIN ratio greater than 1.51 for C-11-MET PET and 58 +/- 26.7 mo in those with a TIN ratio less than 1.51 (P = 0.03). Among the LGGs, median survival was lower in patients with a mean TIN ratio greater than 1.51 for C-11-MET PET (16 +/- 10 mo; 95% confidence interval, 1-36 mo) than in those with a TIN ratio less than 1.51 (P = 0.04). No significant difference in survival in LGGs was based on F-18-FDG uptake and MRI contrast enhancement. Conclusion: C-11-MET PET can predict prognosis in gliomas and is better than F-18-FDG PET and MRI in predicting survival in LGGs. C1 [Singhal, Tarun; Narayanan, Tanjore K.; Jacobs, Martin P.; Bal, Chandrashekhar; Mantil, Joseph C.] Wright State Univ, Charles F Kettering Mem Hosp, Dept Nucl Med PET, Dayton, OH 45429 USA. [Singhal, Tarun] Brigham & Womens Hosp, Boston, MA 02115 USA. [Singhal, Tarun] Massachusetts Gen Hosp, Partners Neurol Program, Boston, MA 02114 USA. RP Mantil, JC (reprint author), Wright State Univ, Charles F Kettering Mem Hosp, Dept Nucl Med PET, 3530 So Blvd, Dayton, OH 45429 USA. EM joseph.mantil@kmcnetwork.org FU RSNA Molecular Imaging Travel Award FX We thank staff members at the Department of Nuclear Medicine/PET at the Charles F. Kettering Memorial Hospital, Kettering, Ohio, for their hard work and dedication. Part of this work was presented at Radiological Society of North America meeting held in Chicago in 2010 and was awarded the RSNA Molecular Imaging Travel Award. No other potential conflict of interest relevant to this article was reported. NR 26 TC 35 Z9 36 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2012 VL 53 IS 11 BP 1709 EP 1715 DI 10.2967/jnumed.111.102533 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 037TC UT WOS:000311128400014 PM 23055534 ER PT J AU Armstrong, AW Wu, J Kovarik, CL Goldyne, ME Oh, DH McKoy, KC Shippy, AM Pak, HS AF Armstrong, April W. Wu, Julie Kovarik, Carrie L. Goldyne, Marc E. Oh, Dennis H. McKoy, Karen C. Shippy, Alison M. Pak, Hon S. TI State of teledermatology programs in the United States SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE live-interactive; practice; real-time; store-and-forward; teledermatology; telehealth; telemedicine ID DERMATOLOGY AB Background: Teledermatology programs in the United States have evolved over the past several decades. No systematic survey of teledermatology programs in the United States is available in peer-reviewed literature. Objective: To provide up-to-date information regarding the state of teledermatology programs in the United States. Methods: Active U.S. teledermatology programs were surveyed in 2011 with regards to practice models, clinical volume, and payment methods. These findings were compared with those from 2003. Results: By January 2012, 37 teledermatology programs were active in the United States. Store-and-forward teledermatology was the most frequent delivery modality offered by 30 (81%) of the programs. The majority of the programs were based at academic institutions (49%), followed by Veterans Administration hospitals (27%), private practice (16%), and health maintenance organizations (HMOs) (8%). The majority of programs (67%) provided services to their home state only, whereas the rest also served additional U. S. states or abroad. The median number of consultations per program was 309 (range, 5-6500) in 2011. The most frequent payer sources were private payers, followed by self-pay, Medicaid, Medicare, and HMOs. Since 2003, with the confirmed discontinuation of 24 previously active programs, the total number of active teledermatology programs in 2011 was 60% of that in 2003. However, the annual consult volume per program nearly doubled for the sustainable programs in 2011. Limitations: Itemized billing information was not uniformly available from all programs. Conclusion: The turnover in teledermatology programs is relatively constant, with an increase in consult volume for sustainable programs. Store-and-forward is the dominant modality of delivery, while hybrid technology model is emerging. (J Am Acad Dermatol 2012;67:939-44.) C1 [Armstrong, April W.] Univ Calif Davis Hlth Syst, Dermatol Clin Res Unit, Dept Dermatol, Sacramento, CA 95816 USA. [Kovarik, Carrie L.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA. [Kovarik, Carrie L.] Univ Penn, Perelman Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. [Goldyne, Marc E.; Oh, Dennis H.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Oh, Dennis H.] San Francisco VA Med Ctr, Dermatol Serv, San Francisco, CA USA. [McKoy, Karen C.] Lahey Clin Fdn, Dept Dermatol, Burlington, MA USA. [Pak, Hon S.] HSP Technol, Clarksburg, MD USA. [Armstrong, April W.; Kovarik, Carrie L.; Goldyne, Marc E.; Oh, Dennis H.; Shippy, Alison M.; Pak, Hon S.] Amer Acad Dermatol, Washington, DC USA. [Armstrong, April W.; Kovarik, Carrie L.; Goldyne, Marc E.; Oh, Dennis H.; McKoy, Karen C.; Shippy, Alison M.; Pak, Hon S.] Amer Telemed Assoc, Washington, DC USA. RP Armstrong, AW (reprint author), Univ Calif Davis Hlth Syst, Dermatol Clin Res Unit, Dept Dermatol, 3301 C St,Suite 1400, Sacramento, CA 95816 USA. EM aprilarmstrong@post.harvard.edu NR 12 TC 25 Z9 25 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 BP 939 EP 944 DI 10.1016/j.jaad.2012.02.019 PG 6 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600053 PM 22459360 ER PT J AU Kroshinsky, D Alloo, A Rothschild, B Cummins, J Tan, J Montecino, R Hoang, MP Duncan, L Mihm, M Sepehr, A AF Kroshinsky, Daniela Alloo, Allireza Rothschild, Brian Cummins, Jordan Tan, Jennifer Montecino, Rafael Hoang, Mai P. Duncan, Lyn Mihm, Martin Sepehr, Alireza TI Necrotizing Sweet syndrome: A new variant of neutrophilic dermatosis mimicking necrotizing fasciitis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE acute febrile neutrophilic dermatosis; acute necrotizing neutrophilic dermatosis; atypical Sweet syndrome; frozen section; myonecrotic Sweet; necrotizing fasciitis; necrotizing Sweet syndrome; neutrophilic dermatosis; pathergy; subcutaneous Sweet syndrome; Sweet syndrome ID PANNICULITIS; LEUKEMIA; DISEASE; MYELODYSPLASIA AB Background: We report a series of patients initially given the diagnosis of necrotizing fasciitis whose course progressed despite surgical debridement, antibiotic therapy, or both, but who responded rapidly to systemic corticosteroids. Objective: We sought to evaluate the clinical data, histopathologic and microbiology information, and treatment course of this unusual entity. Methods: This was a descriptive study/case series. Results: Three immunocompromised patients who presented with signs and symptoms of necrotizing fasciitis were included. They appeared septic, failed multiple courses of antibiotics, demonstrated pathergy, and two of them underwent extensive surgical debridement. None of the cases yielded a microbial source. Dermatologic consultation and histopathology confirmed deep Sweet syndrome in all cases, with marked necrosis of the soft tissue-including myonecrosis-in the two patients with debridement. All patients responded rapidly to high-dose systemic corticosteroids. Limitations: To our knowledge, this is the first report of this unusual presentation; there are a limited number of cases. Conclusion: We propose that these cases represent a new variant of neutrophilic dermatosis: "necrotizing Sweet syndrome," an acute necrotizing neutrophilic dermatosis. This subtype is also characterized by the rapid onset of progressive erythematous, warm, edematous cutaneous lesions with deep-tissue neutrophilic infiltration and soft-tissue necrosis, in the absence of infectious cause. Awareness of this entity and early dermatologic consultation is critical as debridement results in expansion of the process, resulting in additional and aggressive resectionea vicious cycle with significant possible morbidity. (J Am Acad Dermatol 2012;67:945-54.) C1 [Kroshinsky, Daniela; Rothschild, Brian; Cummins, Jordan; Tan, Jennifer] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Montecino, Rafael] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Hoang, Mai P.; Duncan, Lyn; Mihm, Martin; Sepehr, Alireza] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kroshinsky, Daniela; Alloo, Allireza; Rothschild, Brian; Cummins, Jordan; Tan, Jennifer; Montecino, Rafael; Hoang, Mai P.; Duncan, Lyn; Mihm, Martin; Sepehr, Alireza] Harvard Univ, Sch Med, Boston, MA USA. RP Sepehr, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM asepehr@bidmc.harvard.edu NR 26 TC 8 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 BP 945 EP 954 DI 10.1016/j.jaad.2012.02.024 PG 10 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600054 PM 22445215 ER PT J AU Gimbel, DC Sohani, AR Busarla, SVP Kirimi, JM Sayed, S Okiro, P Nazarian, RM AF Gimbel, Devon C. Sohani, Aliyah R. Busarla, Satya Vara Prasad Kirimi, Jesca Muthoni Sayed, Shahin Okiro, Patricia Nazarian, Rosalynn M. TI A static-image telepathology system for dermatopathology consultation in East Africa: The Massachusetts General Hospital Experience SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE cost-effective; dermatopathology consultation; resource-poor setting; static-image; telepathology ID FROZEN-SECTION DIAGNOSIS; OF-THE-ART; ROBOTIC TELEPATHOLOGY; VIRTUAL MICROSCOPY; SKIN SPECIMENS; TELEDERMATOPATHOLOGY; PATHOLOGY; ACCURACY; TELECYTOLOGY; FEASIBILITY AB Background: The histologic diagnosis of skin lesions in the developing world is complicated by the shortage of pathologists with subspecialty training in dermatopathology, limited access to ancillary diagnostic testing, and costly referrals for expert glass slide consultation in challenging cases. Objective: In this study we evaluate the feasibility of a static-image telepathology platform in Africa for performing accurate dermatopathology consultations. Methods: A static-image telepathology platform using the iPath server was utilized by referring pathologists in 4 African hospitals. Diagnostic interpretations were provided by Massachusetts General Hospital dermatopathologists at no cost. The diagnostic accuracy and interobserver correlation was evaluated. Results: The static histopathologic images were diagnostic in 22 of 29 (76%) cases. Diagnostic accuracy between static image and glass slide diagnosis in 22 cases was 91%, ranging from 86% to 95% according to years of dermatopathology subspecialty expertise. Comparison with the glass slides showed that the telepathology diagnosis was limited by inappropriate field selection in only one case. Interobserver concordance between two pathologists was high (K = 0.86) suggesting that this platform is easy to use with minimal training of both referring and consulting pathologists. Limitations: Concordance between conventional microscopy and static image telepathology was performed in 22 of 29 cases for which glass slides were received. Interobserver concordance was performed for two pathologists. Conclusion: Static-image telepathology is a feasible means of rendering diagnoses on dermatopathology cases and is a cost-effective technology for obtaining much-needed second opinions in resource-poor settings. (J Am Acad Dermatol 2012;67:997-1007.) C1 [Gimbel, Devon C.; Sohani, Aliyah R.; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Gimbel, Devon C.; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Busarla, Satya Vara Prasad] Aga Khan Hosp, Dept Pathol, Kisumu, Kenya. [Sayed, Shahin] Aga Khan Univ Hosp, Dept Pathol, Nairobi, Kenya. [Okiro, Patricia] Aga Khan Hosp, Dept Pathol, Mombasa, Kenya. [Kirimi, Jesca Muthoni] Aga Khan Hosp, Dept Pathol, Dar Es Salaam, Tanzania. RP Nazarian, RM (reprint author), Massachusetts Gen Hosp, Pathol Serv, 55 Fruit St,WRN 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org OI Nazarian, Rosalynn/0000-0003-4003-7193; Sayed, Shahin/0000-0002-3472-511X FU Aga Khan Health Board, USA at the Aga Khan University Hospitals in East Africa; Aga Khan Foundation, USA at the Aga Khan University Hospital in East Africa FX The authors are grateful to the Massachusetts General Hospital Pathology Service for the gift of time and equipment and the Aga Khan Health Board, USA and the Aga Khan Foundation, USA for their support of the telepathology system at the Aga Khan University Hospitals in East Africa. NR 31 TC 11 Z9 12 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 BP 997 EP 1007 DI 10.1016/j.jaad.2011.12.036 PG 11 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600061 PM 22341607 ER PT J AU Corey, KC Garshick, MK Dejsuphong, V Lima, XT Kimball, AB AF Corey, Kristen C. Garshick, Marisa Kardos Dejsuphong, Voraphat Lima, Xinaida T. Kimball, Alexandra B. TI Skin carotenoid levels are not associated with risk of nonmelanoma skin cancer: Response to "Supplement use and the risk of cutaneous squamous cell carcinoma" SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID PREVENTION; TRIAL C1 [Dejsuphong, Voraphat; Kimball, Alexandra B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Corey, Kristen C.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Garshick, Marisa Kardos] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lima, Xinaida T.] Univ Estadual Campinas, Dept Clin Pathol, Sao Paulo, Brazil. [Lima, Xinaida T.] Univ Estadual Campinas, Dept Dermatol, Sao Paulo, Brazil. [Kimball, Alexandra B.] Harvard Univ, Sch Med, Boston, MA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St,Suite 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 5 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 BP 1071 EP 1072 DI 10.1016/j.jaad.2012.03.038 PG 3 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600071 PM 23062892 ER PT J AU Tang, JY Fu, T Lau, C Oh, DH Bikle, DD Asgari, MM AF Tang, Jean Y. Fu, Teresa Lau, Christopher Oh, Dennis H. Bikle, Daniel D. Asgari, Maryam M. TI Vitamin D in cutaneous carcinogenesis Part I SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE 25(OH)D levels; cholecalciferol; supplements; vitamin D; ultraviolet radiation ID SUN PROTECTION FACTOR; CELL LUNG-CANCER; SERUM 25-HYDROXYVITAMIN-D LEVELS; RANDOMIZED CONTROLLED-TRIAL; PRIMARY HUMAN KERATINOCYTES; NONMELANOMA SKIN-CANCER; D-ENDOCRINE SYSTEM; BODY-MASS INDEX; D DEFICIENCY; UNITED-STATES AB Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer. (J Am Acad Dermatol 2012;67:803.e1-12.) C1 [Tang, Jean Y.; Fu, Teresa] Stanford Univ, Dept Dermatol, Redwood City, CA 94305 USA. [Lau, Christopher; Asgari, Maryam M.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Oh, Dennis H.; Bikle, Daniel D.; Asgari, Maryam M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Oh, Dennis H.; Bikle, Daniel D.] San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA USA. [Bikle, Daniel D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Tang, JY (reprint author), Stanford Univ, Dept Dermatol, 450 Broadway,Pavil C,MC 5334, Redwood City, CA 94305 USA. EM tangy@stanford.edu RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23 AR 051037-01, K23 AR 056736-01]; Damon Runyon Clinical Investigator Award FX Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K23 AR 051037-01 (Dr Asgari) and K23 AR 056736-01 (Dr Tang) and the Damon Runyon Clinical Investigator Award (Dr Tang). NR 121 TC 3 Z9 3 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 AR 803.e1 DI 10.1016/j.jaad.2012.05.044 PG 12 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600037 PM 23062903 ER PT J AU Tang, JY Fu, T Lau, C Oh, DH Bikle, DD Asgari, MM AF Tang, Jean Y. Fu, Teresa Lau, Christopher Oh, Dennis H. Bikle, Daniel D. Asgari, Maryam M. TI Vitamin D in cutaneous carcinogenesis Part II SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE 25(OH)D levels; basal cell carcinoma; melanoma; nonmelanoma skin cancer; vitamin D; vitamin D receptor; squamous cell carcinoma; sunlight ID BASAL-CELL CARCINOMAS; PRIMARY HUMAN KERATINOCYTES; NONMELANOMA SKIN-CANCER; INDUCED DNA-DAMAGE; MALIGNANT-MELANOMA; D-RECEPTOR; IN-VITRO; 1,25-DIHYDROXYVITAMIN D-3; MOUSE SKIN; D ANALOGS AB The role of vitamin D in health maintenance and disease prevention in fields ranging from bone metabolism to cancer is currently under intensive investigation. A number of epidemiologic studies have suggested that vitamin D may have a protective effect on cancer risk and cancer-associated mortality. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar risk reducing effect. Potential mechanisms of action include inhibition of the hedgehog signaling pathway and upregulation of nucleotide excision repair enzymes. The key factor complicating the association between vitamin D and skin cancer is ultraviolet B radiation. The same spectrum of ultraviolet B radiation that catalyzes the production of vitamin D in the skin also causes DNA damage that can lead to epidermal malignancies. Part II of this continuing medical education article will summarize the literature on vitamin D and skin cancer to identify evidence-based optimal serum levels of vitamin D and to recommend ways of achieving those levels while minimizing the risk of skin cancer. (J Am Acad Dermatol 2012;67:817.e1-11.) C1 [Tang, Jean Y.; Fu, Teresa] Stanford Univ, Dept Dermatol, Redwood City, CA 94305 USA. [Lau, Christopher; Asgari, Maryam M.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Oh, Dennis H.; Bikle, Daniel D.; Asgari, Maryam M.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Bikle, Daniel D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Oh, Dennis H.; Bikle, Daniel D.] San Francisco VA Med Ctr, No Calif Inst Res & Educ, San Francisco, CA USA. RP Tang, JY (reprint author), Stanford Univ, Dept Dermatol, 450 Broadway,Pavil C,MC 5334, Redwood City, CA 94305 USA. EM tangy@stanford.edu RI Asgari, Maryam/O-4947-2016 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K23 AR 051037-01, K23 AR 056736-01]; Damon Runyon Clinical Investigator Award; VA Office of Research and Development Merit Award [I01BX007080] FX Supported by National Institute of Arthritis and Musculoskeletal and Skin Diseases grants K23 AR 051037-01 (Dr Asgari) and K23 AR 056736-01 ( Dr Tang), the Damon Runyon Clinical Investigator Award ( Dr Tang), and the VA Office of Research and Development Merit Award I01BX007080 ( Dr Oh). NR 82 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2012 VL 67 IS 5 PG 11 WC Dermatology SC Dermatology GA 033EI UT WOS:000310776600038 ER PT J AU Farbota, KDM Sodhi, A Bendlin, BB McLaren, DG Xu, GF Rowley, HA Johnson, SC AF Farbota, Kimberly D. M. Sodhi, Aparna Bendlin, Barbara B. McLaren, Donald G. Xu, Guofan Rowley, Howard A. Johnson, Sterling C. TI Longitudinal Volumetric Changes following Traumatic Brain Injury: A Tensor-Based Morphometry Study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Longitudinal studies; Recovery of function; Brain injuries; humans; Neurosciences; Magnetic resonance imaging; Chronic brain injuries; Brain mapping; Apoptosis; Necrosis ID INDUCED AXONAL INJURY; WALLERIAN DEGENERATION; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; ATROPHY; MILD; AXOTOMY; PATHOBIOLOGY; AUTOPHAGY; ANIMALS AB After traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements. (JINS, 2012, 18, 1006-1018) C1 [Farbota, Kimberly D. M.; Sodhi, Aparna; Bendlin, Barbara B.; McLaren, Donald G.; Xu, Guofan; Johnson, Sterling C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53792 USA. [Farbota, Kimberly D. M.; McLaren, Donald G.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Sodhi, Aparna; Bendlin, Barbara B.; Xu, Guofan; Johnson, Sterling C.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Rowley, Howard A.] Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Farbota, KDM (reprint author), William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, J5M-162 CSC,600 Highland Ave, Madison, WI 53792 USA. EM kim.farbota@gmail.com OI Bendlin, Barbara/0000-0002-0580-9875; McLaren, Donald/0000-0002-0566-4610; Johnson, Sterling/0000-0002-8501-545X FU Department of Veterans Affairs; NIH [MH65723, AG000213] FX This study was supported by a Merit Review Grant from the Department of Veterans Affairs, the NIH MH65723 (SCJ), NIH AG000213, and by the facilities and resources of the William S. Middleton Memorial Veterans Hospital. The authors declare no conflict of interest. The assistance of Robert Dempsey, MD, Jack Sherman, PhD, Tisha Kawahara, Taylor Schmitz, Lisa Newman, Amy Hawley, and Erik Kastman is greatly appreciated. We also greatly appreciate the support of researchers and staff at the Waisman Center, University of Wisconsin, Madison, where MR imaging took place. Donald McLaren, PhD, is now affiliated with Harvard University Medical School and the Massachusetts General Hospital, Department of Neurology. Finally, we thank all the patients who took part in this study. The contents of this study do not represent the views of the Department of Veterans Affairs or the United States Government. NR 45 TC 25 Z9 26 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2012 VL 18 IS 6 BP 1006 EP 1018 DI 10.1017/S1355617712000835 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 048IT UT WOS:000311905300008 PM 22883443 ER PT J AU Mitchell, MB Shaughnessy, LW Shirk, SD Yang, FM Atri, A AF Mitchell, Meghan B. Shaughnessy, Lynn W. Shirk, Steven D. Yang, Frances M. Atri, Alireza TI Neuropsychological Test Performance and Cognitive Reserve in Healthy Aging and the Alzheimer's Disease Spectrum: A Theoretically Driven Factor Analysis SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Mild cognitive impairment; Brain reserve; Executive function; Memory function; Dementia; Cognition ID UNIFORM DATA SET; CONSTRUCT-VALIDITY; FIT INDEXES; DEMENTIA; MEMORY; INDIVIDUALS; VARIABLES; CENTERS; DECLINE; BRAIN AB Accurate measurement of cognitive function is critical for understanding the disease course of Alzheimer's disease (AD). Detecting cognitive change over time can be confounded by level of premorbid intellectual function or cognitive reserve and lead to under-or over-diagnosis of cognitive impairment and AD. Statistical models of cognitive performance that include cognitive reserve can improve sensitivity to change and clinical efficacy. We used confirmatory factor analysis to test a four-factor model composed of memory/language, processing speed/executive function, attention, and cognitive reserve factors in a group of cognitively healthy older adults and a group of participants along the spectrum of amnestic mild cognitive impairment to AD (aMCI-AD). The model showed excellent fit for the control group (chi(2) = 100; df = 78; CFI = .962; RMSEA = .049) and adequate fit for the aMCI-AD group (chi(2) = 1750; df = 78; CFI = .932; RMSEA = .085). Although strict invariance criteria were not met, invariance testing to determine if factor structures are similar across groups yielded acceptable absolute model fits and provide evidence in support of configural, metric, and scalar invariance. These results provide further support for the construct validity of cognitive reserve in healthy and memory impaired older adults. (JINS, 2012, 18, 1071-1080) C1 [Mitchell, Meghan B.; Shirk, Steven D.; Atri, Alireza] Edith Nourse Rogers Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, Bedford, MA 01730 USA. [Mitchell, Meghan B.; Shirk, Steven D.; Atri, Alireza] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mitchell, Meghan B.; Shaughnessy, Lynn W.; Yang, Frances M.; Atri, Alireza] Harvard Univ, Sch Med, Boston, MA USA. [Shaughnessy, Lynn W.] Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. [Shaughnessy, Lynn W.] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. [Yang, Frances M.] Hebrew Senior Life, Inst Aging Res, Boston, MA USA. [Yang, Frances M.] Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. RP Mitchell, MB (reprint author), Edith Nourse Rogers Mem Vet Adm Hosp, Geriatr Res Educ & Clin Ctr, 200 Springs Rd,182B, Bedford, MA 01730 USA. EM Meghan.Mitchell2@va.gov OI Atri, Alireza/0000-0003-4405-6973 FU VA Advanced Fellowship in Geriatrics through the New England Geriatric Research Education and Clinical Center (GRECC); NIA [K23AG027171] FX We thank the Clinical, Administrative, and Biostatistics and Bioinformatics Cores of the Massachusetts Alzheimer's Disease Research Center (NIA 5 P50AG05134 Growdon and Hyman), and the Bedford Division of the New England Geriatric Research Education and Clinical Center (GRECC) at the ENRM Veterans Administration (VA) Hospital. Dr. Mitchell is supported by a VA Advanced Fellowship in Geriatrics through the New England Geriatric Research Education and Clinical Center (GRECC). The contents of this study do not represent the views of the Department of Veterans Affairs or the United States Government. We also thank Dr. Daniel Mungas and the Friday Harbor Advanced Psychometric Methods for Cognitive Aging Research workshop (R13AG030995, PI: Dan Mungas), Dr. Joseph Locascio, Dr. Rebecca England, Dr. Dorene Rentz, Dr. Alden Gross, Dr. Richard Jones, and Dr. Liang Yap for providing significant assistance, guidance, teaching, resources and/or helpful comments. Finally, and most importantly, we express our deep gratitude for the commitment of the MADRC UDS Longitudinal Cohort study participants without whose generous contribution and dedication this research would not be possible. This study was funded by NIA K23AG027171 (Atri). The authors have no conflicts of interest with the present study. NR 52 TC 5 Z9 6 U1 1 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2012 VL 18 IS 6 BP 1071 EP 1080 DI 10.1017/S1355617712000859 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 048IT UT WOS:000311905300014 PM 23039909 ER PT J AU Essig, M Dinkel, J Gutierrez, JE AF Essig, Marco Dinkel, Julien Gutierrez, Juan E. TI Use of Contrast Media in Neuroimaging SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA LA English DT Article DE CNS imaging; Contrast media; DSC-perfusion MRI; Dynamic contrast enhanced MRI ID BLOOD-BRAIN-BARRIER; HERPES-SIMPLEX ENCEPHALITIS; MAGNETIZATION-TRANSFER SATURATION; ENHANCED MRI; GADOPENTETATE DIMEGLUMINE; PERFUSION MRI; COMPUTED-TOMOGRAPHY; INTRACRANIAL TUMORS; MALIGNANT GLIOMAS; ISCHEMIC PENUMBRA AB Since their introduction, gadolinium-based contrast media are routinely used in most CNS MR imaging indications. Due to their paramagnetic effect, they significantly shorten the T1 relaxation times of the tissue and are therefore applied to improve the sensitivity and specificity of CNS diseases and to allow a better treatment decision, planning, and follow-up. More recently, contrast media have also been used to allow the measurement of tissue perfusion and to follow the time course of enhancement in dynamic contrast-enhanced imaging studies. Routinely they are used to enhance MR angiography studies. C1 [Essig, Marco] Univ Erlangen Nurnberg, Dept Neuroradiol, D-91054 Erlangen, Germany. [Dinkel, Julien] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gutierrez, Juan E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. RP Essig, M (reprint author), Univ Erlangen Nurnberg, Dept Neuroradiol, Schwabachanlage 6, D-91054 Erlangen, Germany. EM marco.essig@uk-erlangen.de NR 91 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1064-9689 J9 MAGN RESON IMAGING C JI Magn. Reson. Imaging Clin. N. Am. PD NOV PY 2012 VL 20 IS 4 BP 633 EP + DI 10.1016/j.mric.2012.08.001 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 047UE UT WOS:000311866200004 PM 23088943 ER PT J AU Bilgic, B Setsompop, K Cohen-Adad, J Yendiki, A Wald, LL Adalsteinsson, E AF Bilgic, Berkin Setsompop, Kawin Cohen-Adad, Julien Yendiki, Anastasia Wald, Lawrence L. Adalsteinsson, Elfar TI Accelerated diffusion spectrum imaging with compressed sensing using adaptive dictionaries SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion spectrum imaging; compressed sensing; adaptive dictionary ID ALGORITHM; IMAGES; MRI AB Diffusion spectrum imaging offers detailed information on complex distributions of intravoxel fiber orientations at the expense of extremely long imaging times (similar to 1 h). Recent work by Menzel et al. demonstrated successful recovery of diffusion probability density functions from sub-Nyquist sampled q-space by imposing sparsity constraints on the probability density functions under wavelet and total variation transforms. As the performance of compressed sensing reconstruction depends strongly on the level of sparsity in the selected transform space, a dictionary specifically tailored for diffusion probability density functions can yield higher fidelity results. To our knowledge, this work is the first application of adaptive dictionaries in diffusion spectrum imaging, whereby we reduce the scan time of whole brain diffusion spectrum imaging acquisition from 50 to 17 min while retaining high image quality. In vivo experiments were conducted with the 3T Connectome MRI. The root-mean-square error of the reconstructed missing diffusion images were calculated by comparing them to a gold standard dataset (obtained from acquiring 10 averages of diffusion images in these missing directions). The root-mean-square error from the proposed reconstruction method is up to two times lower than that of Menzel et al.'s method and is actually comparable to that of the fully-sampled 50 minute scan. Comparison of tractography solutions in 18 major white-matter pathways also indicated good agreement between the fully-sampled and 3-fold accelerated reconstructions. Further, we demonstrate that a dictionary trained using probability density functions from a single slice of a particular subject generalizes well to other slices from the same subject, as well as to slices from other subjects. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Bilgic, Berkin; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Setsompop, Kawin; Cohen-Adad, Julien; Yendiki, Anastasia; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Setsompop, Kawin; Cohen-Adad, Julien; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA USA. [Wald, Lawrence L.; Adalsteinsson, Elfar] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Bilgic, B (reprint author), MIT, Dept Elect Engn & Comp Sci, Room 36-776A,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM berkin@mit.edu RI Setsompop, Kawin/P-1464-2014; bilgic, berkin/P-1811-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; FU NIH [NIH R01 EB007942, NIBIB K99EB012107, NIBIB R01EB006847, K99/R00 EB008129, NCRR P41RR14075, U01MH093765]; Siemens Healthcare; Siemens-MIT Alliance; MIT-CIMIT Medical Engineering Fellowship FX Grant sponsor: NIH; Grant numbers: NIH R01 EB007942, NIBIB K99EB012107, NIBIB R01EB006847, K99/R00 EB008129, NCRR P41RR14075, U01MH093765 (NIH Blueprint for Neuroscience Research: The Human Connectome project); Grant sponsors: Siemens Healthcare, Siemens-MIT Alliance, MIT-CIMIT Medical Engineering Fellowship. NR 19 TC 23 Z9 23 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2012 VL 68 IS 6 BP 1747 EP 1754 DI 10.1002/mrm.24505 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041JR UT WOS:000311398600008 PM 23008145 ER PT J AU Qian, YX Zhao, TJ Wiggins, GC Wald, LL Zheng, H Weimer, J Boada, FE AF Qian, Yongxian Zhao, Tiejun Wiggins, Graham C. Wald, Lawrence L. Zheng, Hai Weimer, Jonathan Boada, Fernando E. TI Sodium imaging of human brain at 7 T with 15-channel array coil SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE sodium MRI; whole-body 7 T MRI; phased array coil; signal-to-noise ratio ID PHASED-ARRAY; TUMORS AB Signal-to-noise ratio (SNR) is a major challenge to sodium magnetic resonance imaging. Phased array coils have been shown significantly improving SNR in proton imaging over volume coils. This study investigates SNR advantage of a 15-channel array head coil (birdcage volume coil for transmit/receive and 15-channel array insert for receive-only) in sodium imaging at 7 T. Phantoms and healthy human brains were scanned on a whole-body 7 T magnetic resonance imaging scanner using a customer-developed pulse sequence with the twisted projection imaging trajectory. Noise-only images were acquired with blanked radiofrequency excitations for noise measurement on a pixel basis. SNR was calculated on the root of sum-of-squares images. When compared with the volume coil, the 15-channel array produced SNR more than doubled at the periphery and slightly increased at the center of the phantoms and human brains. Decorrelation of noise across channels of the array coil extended the SNR-doubled region into deep area of the brain. The spatial modulation of element sensitivities on the sum-of-squares combined image was removed by performing self-calibrated sensitivity encoding parallel image reconstruction and uniform image intensity across entire field of view was attained. The 15-channel array coil is an efficient tool to substantially improve SNR in sodium imaging on human brain. Magn Reson Med, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Qian, Yongxian; Boada, Fernando E.] Univ Pittsburgh, MR Res Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. [Qian, Yongxian; Zheng, Hai; Weimer, Jonathan; Boada, Fernando E.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Zhao, Tiejun] Siemens Med Solut USA, Pittsburgh, PA USA. [Wiggins, Graham C.] NYU, Dept Radiol, Langone Med Ctr, New York, NY 10016 USA. [Wald, Lawrence L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Qian, YX (reprint author), Univ Pittsburgh, MR Res Ctr, Dept Radiol, UPMC Presbyterian B804,200 Lothrop St, Pittsburgh, PA 15213 USA. EM qiany@upmc.edu RI Wald, Lawrence/D-4151-2009 FU NIH [R01 CA106840]; Department of Radiology Development Fund, University of Pittsburgh FX Grant sponsor: NIH; Grant number: R01 CA106840; Grant sponsor: Department of Radiology Development Fund, University of Pittsburgh. NR 17 TC 15 Z9 15 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2012 VL 68 IS 6 BP 1808 EP 1814 DI 10.1002/mrm.24192 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 041JR UT WOS:000311398600014 PM 22377960 ER PT J AU Morley, JF Duda, JE AF Morley, James F. Duda, John E. TI Head injury and the risk of Parkinson's disease SO MOVEMENT DISORDERS LA English DT Editorial Material ID ALPHA-SYNUCLEIN; YOUNG-ONSET; EPIDEMIOLOGY; POPULATION; TRAUMA; ETIOLOGY; SMOKING; HISTORY; BRAIN; DRUGS C1 [Morley, James F.] Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Morley, JF (reprint author), Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM morleyj@uphs.upenn.edu NR 41 TC 0 Z9 0 U1 1 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2012 VL 27 IS 13 BP 1592 EP 1594 DI 10.1002/mds.25230 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 045KU UT WOS:000311695500002 PM 23192921 ER PT J AU Miranda, M Jung, HH Danek, A Walker, RH AF Miranda, Marcelo Jung, Hans H. Danek, Adrian Walker, Ruth H. TI The chorea of McLeod syndrome: Progression to hypokinesia SO MOVEMENT DISORDERS LA English DT Letter ID PHENOTYPE C1 [Miranda, Marcelo] Clin Las Condes, Dept Neurol, Santiago, Chile. [Jung, Hans H.] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland. [Danek, Adrian] Univ Munich, Neurol Klin, Munich, Germany. [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu RI Danek, Adrian/G-7339-2011 OI Danek, Adrian/0000-0001-8857-5383 NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2012 VL 27 IS 13 BP 1701 EP 1702 DI 10.1002/mds.25224 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 045KU UT WOS:000311695500027 PM 23192927 ER PT J AU Tilden, V Corless, I Dahlin, C Ferrell, B Gibson, R Lentz, J AF Tilden, Virginia Corless, Inge Dahlin, Constance Ferrell, Betty Gibson, Rosemary Lentz, Judy TI Advance care planning as an urgent public health concern SO NURSING OUTLOOK LA English DT Editorial Material C1 [Tilden, Virginia] Univ Nebraska Med Ctr, Coll Nursing, Omaha, NE 68198 USA. [Corless, Inge] MGH Inst Hlth Profess, Charlestown, MA USA. [Dahlin, Constance] Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. [Ferrell, Betty] City Hope Natl Med Ctr, Duarte, CA USA. [Lentz, Judy] Hosp & Palliat Nurses Assoc, Pittsburgh, PA USA. RP Tilden, V (reprint author), Univ Nebraska Med Ctr, Coll Nursing, 985330 Nebraska Med Ctr, Omaha, NE 68198 USA. EM vtilden@unmc.edu OI Corless, Inge/0000-0003-0438-2037 NR 3 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD NOV-DEC PY 2012 VL 60 IS 6 BP 418 EP 419 DI 10.1016/j.outlook.2012.09.003 PG 2 WC Nursing SC Nursing GA 043EU UT WOS:000311526500015 ER PT J AU Chabner, BA AF Chabner, Bruce A. TI That Old Devil Moon SO ONCOLOGIST LA English DT Editorial Material ID CANCER C1 [Chabner, Bruce A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Director Clin Res, Boston, MA USA. RP Chabner, BA (reprint author), 10 N Grove St,LRH 214, Boston, MA 02114 USA. EM bchabner@partners.org NR 5 TC 0 Z9 0 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2012 VL 17 IS 11 BP 1349 EP 1350 DI 10.1634/theoncologist.2012-0392 PG 2 WC Oncology SC Oncology GA 045XS UT WOS:000311730700001 PM 23070694 ER PT J AU Ou, SHI Bartlett, CH Mino-Kenudson, M Cui, J Iafrate, AJ AF Ou, Sai-Hong Ignatius Bartlett, Cynthia Huang Mino-Kenudson, Mari Cui, Jean Iafrate, A. John TI Crizotinib for the Treatment of ALK-Rearranged Non-Small Cell Lung Cancer: A Success Story to Usher in the Second Decade of Molecular Targeted Therapy in Oncology SO ONCOLOGIST LA English DT Article DE Crizotinib; ALK inhibitor; MET inhibitor; ROS1 inhibitor; Chromosomal rearrangements; Receptor tyrosine kinase fusion positive malignancies; Non-small cell lung cancer (NSCLC) ID ANAPLASTIC LYMPHOMA KINASE; RECEPTOR TYROSINE KINASE; EML4-ALK FUSION GENE; IN-SITU-HYBRIDIZATION; NON-HODGKINS-LYMPHOMA; C-MET RECEPTOR; WILD-TYPE EGFR; NEVER-SMOKERS; ACTIVATING MUTATIONS; GROWTH-FACTOR AB Crizotinib, an ALK/MET/ROS1 inhibitor, was approved by the U. S. Food and Drug Administration for the treatment of anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) in August 2011, merely 4 years after the first publication of ALK-rearranged NSCLC. The crizotinib approval was accompanied by the simultaneous approval of an ALK companion diagnostic fluorescent in situ hybridization assay for the detection of ALK-rearranged NSCLC. Crizotinib continued to be developed as an ALK and MET inhibitor in other tumor types driven by alteration in ALK and MET. Crizotinib has recently been shown to be an effective ROS1 inhibitor in ROS1-rearranged NSCLC, with potential future clinical applications in ROS1-rearranged tumors. Here we summarize the heterogeneity within the ALK- and ROS1-rearranged molecular subtypes of NSCLC. We review the past and future clinical development of crizotinib for ALK-rearranged NSCLC and the diagnostic assays to detect ALK-rearranged NSCLC. We highlight how the success of crizotinib has changed the paradigm of future drug development for targeted therapies by targeting a molecular-defined subtype of NSCLC despite its rarity and affected the practice of personalized medicine in oncology, emphasizing close collaboration between clinical oncologists, pathologists, and translational scientists. The Oncologist 2012; 17:1351-1375 C1 [Ou, Sai-Hong Ignatius] Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, Orange, CA 92868 USA. [Bartlett, Cynthia Huang] Pfizer Oncol, New York, NY USA. [Mino-Kenudson, Mari; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cui, Jean] Pfizer Global Res, La Jolla, CA USA. RP Ou, SHI (reprint author), Univ Calif Irvine, Med Ctr, Chao Family Comprehens Canc Ctr, 101 City Dr,Bldg 56,RT81, Orange, CA 92868 USA. EM ignatius.ou@uci.edu FU Pfizer FX We thank Keith Wilner (Pfizer Global Research, La Jolla, CA, USA) for shepherding the initial and ongoing clinical development of crizotinib. This work was supported by funding from Pfizer. Editorial assistance was provided by Martin Quinn at Acumed (Tytherington, U.K.). NR 181 TC 94 Z9 102 U1 2 U2 21 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD NOV PY 2012 VL 17 IS 11 BP 1351 EP 1375 DI 10.1634/theoncologist.2012-0311 PG 25 WC Oncology SC Oncology GA 045XS UT WOS:000311730700002 PM 22989574 ER PT J AU Davis, EL Oh, B Butow, PN Mullan, BA Clarke, S AF Davis, Esther L. Oh, Byeongsang Butow, Phyllis N. Mullan, Barbara A. Clarke, Stephen TI Cancer Patient Disclosure and Patient-Doctor Communication of Complementary and Alternative Medicine Use: A Systematic Review SO ONCOLOGIST LA English DT Review DE Complementary and alternative medicine; Cancer; Disclosure; Doctor-patient relations ID BREAST-CANCER; PROSTATE-CANCER; THERAPY USE; PREVALENCE; WOMEN; PHYSICIANS; PATTERNS; SURVIVORS; ONCOLOGY AB Objective. To explore the nondisclosure of complementary and alternative medicine (CAM) use among cancer patients, including reasons for and outcomes from nondisclosure of CAM use, within the context of patient-doctor communication. Method. A systematic review was conducted exploring investigations surrounding the communication of CAM use for patients with cancer published until August 2011. Results. A total of 21 studies were located, which reported a prevalence of CAM use among patients with cancer ranging between 11% and 95%; of these patients, 20% to 77% did not disclose their CAM use. The main reasons for nondisclosure were the doctor's lack of inquiry; patient's anticipation of the doctor's disapproval, disinterest, or inability to help; and patient's perception that disclosure of CAM use is irrelevant to their conventional care. There is some evidence to suggest that patient-doctor communication about the use of CAM was associated with an enhanced patient-doctor relationship and higher patient satisfaction. Conclusions. Although the use of CAM by patients with cancer is high, patients frequently fail to disclose its use to their health professionals for reasons emanating from both sides of the dyadic patient-doctor relationship. Because a substantial proportion of patients with cancer may use CAM and there is potential for herb- or vitamin-drug interactions, further research in patient-doctor communication about CAM is necessary to maintain patient safety and wellbeing. The development of effective interventions to improve the disclosure of CAM use should be an integral part of this future research. The Oncologist 2012; 17: 1475-1481 C1 [Davis, Esther L.; Oh, Byeongsang; Butow, Phyllis N.; Mullan, Barbara A.] Univ Sydney, Ctr Med Psychol & Evidence Based Decis Making, Sydney, NSW 2006, Australia. [Oh, Byeongsang; Clarke, Stephen] Univ Sydney, Royal N Shore Hosp, Sydney Med Sch, Dept Med Oncol, St Leonards, NSW 2065, Australia. [Oh, Byeongsang] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Davis, EL (reprint author), Univ Sydney, Ctr Med Psychol & Evidence Based Decis Making, Room 158,Transient Bldg F12, Sydney, NSW 2006, Australia. EM esther.davis@sydney.edu.au OI Mullan, Barbara/0000-0002-0177-8899 NR 48 TC 51 Z9 53 U1 7 U2 28 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD NOV PY 2012 VL 17 IS 11 BP 1475 EP 1481 DI 10.1634/theoncologist.2012-0223 PG 7 WC Oncology SC Oncology GA 045XS UT WOS:000311730700016 PM 22933591 ER PT J AU Sarris, J Fava, M Schweitzer, I Mischoulon, D AF Sarris, J. Fava, M. Schweitzer, I. Mischoulon, D. TI St John's Wort (Hypericum perforatum) versus Sertraline and Placebo in Major Depressive Disorder: Continuation Data from a 26-Week RCT SO PHARMACOPSYCHIATRY LA English DT Article DE St John's wort; Hypericum perforatum; sertraline; antidepressants; randomized controlled trial; depression; herbal medicine ID RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND; TOLERABILITY; SEVERITY; EFFICACY; SCALE; SSRIS AB Introduction: Hypericum perforatum (St John's wort: SJW) has been extensively studied as an antidepressant in short-term trials, however little research has been conducted on longer-term efficacy. Methods: Our objective was to analyze the continuation data from a 26-week randomized, double-blind, controlled study of SJW (LI-160) vs. sertraline and placebo in major depressive disorder. 124 participant "responders" continued treatment after week 8, until week 26. They continued randomly assigned SJW (900-1500 mg), sertraline (50-100 mg) or matching placebo. Results: At week 26, on the primary outcome, Hamilton depression rating scale (HAM-D) completer scores were: SJW (6.6 +/- 4.5), sertraline (7.1 +/- 5.4) and placebo (5.7 +/- 5.4) with a significant effect for time (p=0.036). Comparisons between all treatments were however non-significant (p=0.61). This effect was mirrored on the other outcomes: the BDI, CGI-severity, CGI-improvement, and on intention-to-treat analyses. Conclusion: While the continuation data revealed an equivocal outcome between treatments at week 26, both SJW and sertraline were still therapeutically effective, with a pronounced "placebo-effect" impeding a significant result at week 26. C1 [Sarris, J.] Univ Melbourne, Dept Psychiat, Melbourne Clin, Melbourne, Vic, Australia. [Sarris, J.] Swinburne Univ Technol, Ctr Human Psychopharmacol, Melbourne, Vic, Australia. [Fava, M.; Mischoulon, D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02115 USA. RP Sarris, J (reprint author), Univ Melbourne, Dept Psychiat, Melbourne Clin, 2 Salisbury St, Melbourne, Vic, Australia. EM jsarris@unimelb.edu.au FU MGH Depression Clinical and Research Program's clinical practice revenues; National Institute of Mental Health (NIMH); National Center for Complementary and Alternative Medicine (NCCAM); Australian National Health & Medical Research Council fellowship (NHMRC) [628875]; Integria Health; Society for Medicinal Plant and Natural Product Research; Pfizer; Alkermes, Inc.; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research Development; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Institute of Drug Abuse (NIDA); Novartis AG; PamLab, LLC.; Pfizer Inc.; Pharmavite(R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Synthelabo; Wyeth-Ayerst Laboratories; Nordic Naturals; Ganeden; Fisher Wallace; Bowman Family Foundation; [N01 MH070007] FX This reanalysis is supported in part by the MGH Depression Clinical and Research Program's clinical practice revenues. The authors thank the members of the Hypericum Depression Trial Study Group for allowing us access to the original database from their clinical trial. Information about the database and how to obtain access to it is available at: http://www.nimh.nih.gov/trials/datasets/nimh-procedures-for-requesting-d ata-sets.shtml. The grant number of the parent study is N01 MH070007. The ClinicalTrials.gov Identifier is NCT00005013. The Placebo-Controlled Clinical Trial of a Standardized Extract of Hypericum perforatum in Major Depressive Disorder was conducted and supported by the National Institute of Mental Health (NIMH) and the National Center for Complementary and Alternative Medicine (NCCAM) in collaboration with the study investigators. This manuscript reflects the views of the authors and may not reflect the opinions or views of all the study investigators, the NIMH, or the NCCAM. Study medications were donated by Lichtwer Pharma and Pfizer. Dr. Jerome Sarris is funded by an Australian National Health & Medical Research Council fellowship (NHMRC funding ID 628875), in a strategic partnership with The University of Melbourne and The Centre for Human Psychopharmacology at Swinburne University of Technology.; No direct conflicts of interest noted. Dr. Sarris is involved in academic research of natural products in the treatment of psychiatric disorders. This publication is not supported by any direct funding and no potential financial benefit is expected as a result of this publication. Dr. Sarris has received travel grant funding from Integria Health, Society for Medicinal Plant and Natural Product Research, and Pfizer. Dr. Fava has received research support from: Alkermes, Inc.; AstraZeneca; BioResearch; BrainCells Inc.; Bristol-Myers Squibb; CeNeRx BioPharma; Clinical Trials Solutions, LLC; Clintara, LLC; Covance; Covidien; Eli Lilly and Company; EnVivo Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Forest Pharmaceuticals, Inc.; Ganeden Biotech, Inc.; GlaxoSmithKline; Icon Clinical Research; i3 Innovus/Ingenix; Johnson & Johnson Pharmaceutical Research & Development; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Novartis AG; PamLab, LLC.; Pfizer Inc.; Pharmavite (R) LLC; Photothera; Roche Pharmaceuticals; RCT Logic, LLC; Sanofi-Aventis US LLC; Synthelabo; Wyeth-Ayerst Laboratories. He has served as Advisor/Consultant to: Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells Inc; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon, Inc.; Clinical Trials Solutions, LLC; CNS Response, Inc.; Compellis Pharmaceuticals; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co. Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai Inc.; Eli Lilly and Company; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson Pharmaceutical Research & Development, LLC; Knoll Pharmaceuticals Corp.; Labopharm Inc.; Lorex Pharmaceuticals; Lundbeck Inc.; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; Neuronetics, Inc.; Next Wave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pam Lab, LLC.; Pfizer Inc.; PharmaStar; Pharmavite LLC.; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals, Inc.; Puretech Ventures; PsychoGenics; Psylin Neurosciences, Inc.; Rexahn Pharmaceuticals, Inc.; Ridge Diagnostics, Inc.; Roche; RCT Logic, LLC; Sanofi-Aventis US LLC.; Sepracor Inc.; Servier Laboratories; Schering-Plough Corporation; Solvay Pharmaceuticals, Inc.; Somaxon Pharmaceuticals, Inc.; Somerset Pharmaceuticals, Inc.; Sunovion Pharmaceuticals; Supernus Pharmaceuticals, Inc.; Synthelabo; Takeda Pharmaceutical Company Limited; Tal Medical, Inc.; Tetragenex Pharmaceuticals, Inc.; Trans Form Pharmaceuticals, Inc.; Transcept Pharmaceuticals, Inc.; Vanda Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories He has received speaking and publishing honoraria from: Adamed, Co; Advanced Meeting Partners; American Psychiatric Association; American Society of Clinical Psychopharmacology; AstraZeneca; Belvoir Media Group; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Cephalon, Inc.; ; CME Institute/Physicians Postgraduate Press, Inc.; Eli Lilly and Company; Forest Pharmaceuticals, Inc.; GlaxoSmithKline; Imedex, LLC; MGH Psychiatry Academy/Primedia; MGH Psychiatry Academy/Reed Elsevier; Novartis AG; Organon Pharmaceuticals; Pfizer Inc.; PharmaStar; United BioSource, Corp.; Wyeth-Ayerst Laboratories; Equity Holdings: Compellis. Royalty/patent, other income: Patent for Sequential Parallel Comparison Design (SPCD) and patent application for a combination of azapirones and bupropion in Major Depressive Disorder (MDD), copyright royalties for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER. Patent for research and licensing of SPCD with RCT Logic; Lippincott, Williams & Wilkins; World Scientific Publishing Co. Pte. Ltd. Dr Schweitzer has received speaking honoraria from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, Pfizer, Servier, and Janssen-Cilag; consultancy fees from AstraZeneca, Eli Lilly, Lundbeck, Wyeth, and Pfizer; and educational or research grants, sponsorships, or donations from Wyeth, Lundbeck, and Bristol-Myers Squibb. Dr. Mischoulon has received research support from Nordic Naturals, Ganeden, Fisher Wallace, and the Bowman Family Foundation. He has served as an advisor/consultant to Bristol-Meyers Squibb Company, and ICON. He has received speaking honoraria from Nordic Naturals, and writing honoraria from Pam lab. He has received royalties from Back Bay Scientific for PMS Escape, and from Lippincott Williams & Wilkins for textbook "Natural Medications for Psychiatric Disorders: Considering the Alternatives" (David Mischoulon and Jerrold F Rosenbaum, Eds.). He has received honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website www.mghcme.org. No payment from any individual entity or company has exceeded $10000/year. NR 16 TC 11 Z9 11 U1 2 U2 51 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0176-3679 J9 PHARMACOPSYCHIATRY JI Pharmacopsychiatry PD NOV PY 2012 VL 45 IS 7 BP 275 EP 278 DI 10.1055/s-0032-1306348 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 045PN UT WOS:000311709400003 PM 22592504 ER PT J AU Sonpavde, G Kantoff, PW AF Sonpavde, Guru Kantoff, Philip W. TI Immunotherapy for Castration-Resistant Prostate Cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Immunotherapy; Castration-resistant; Prostate cancer; Sipuleucel-T; CTLA-4; PROSTVAC-VF TRICOM; Immune response; Overall survival ID PHASE-I TRIAL; MONOCLONAL-ANTIBODY J591; DOSE-ESCALATION TRIAL; MEMBRANE ANTIGEN; TUMOR-CELLS; CELLULAR IMMUNOTHERAPY; SIPULEUCEL-T; SOLID TUMORS; ACID-PHOSPHATASE; LISTERIA-MONOCYTOGENES AB The improved survival with sipuleucel-T, an autologous antigen-presenting cell based agent, for the treatment of patients with metastatic asymptomatic and minimally symptomatic castration-resistant prostate cancer supports immunotherapy as a valid approach. Also, multiple novel immunotherapeutic approaches are undergoing vigorous investigation. T-lymphocyte checkpoint blockade and poxvirus-based prime-boost approaches are in phase III evaluation. Other immunotherapeutic platforms undergoing early investigation include radioimmunoconjugates and adenovirus-based, DNA-based, and Listeria-based approaches. The development of predictive markers for immune response that translate into improved long-term outcomes is important. This article reviews the emerging data and the unique strengths and weaknesses of these approaches. C1 [Kantoff, Philip W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02215 USA. [Sonpavde, Guru] UAB, Dept Med, Sect Med Oncol, Comprehens Canc Ctr, Birmingham, AL 35294 USA. RP Kantoff, PW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM philip_kantoff@dfci.harvard.edu FU Bellicum Pharmaceuticals; BMS FX Relevant disclosures. Guru Sonpavde: Research funding to institution from Bellicum Pharmaceuticals and BMS; speaker for Dendreon. Philip W. Kantoff: Paid consultant to Bellicum Pharmaceuticals, Dendreon, and BN-IT. NR 109 TC 4 Z9 4 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 2012 VL 39 IS 4 BP 465 EP + DI 10.1016/j.ucl.2012.07.004 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 047UK UT WOS:000311866800005 PM 23084524 ER PT J AU Van Allen, EM Pomerantz, M AF Van Allen, Eliezer M. Pomerantz, Mark TI Moving Toward Personalized Medicine in Castration-Resistant Prostate Cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Castration-resistant prostate cancer; CRPC; Personalized medicine; Androgen receptor; ETS; Next-generation sequencing ID ANTITUMOR-ACTIVITY; PTEN; GENE; ANTIANDROGEN; ABIRATERONE; INHIBITION; DOCETAXEL; MELANOMA; THERAPY; BRAF AB Recent advances in research technologies have allowed improved molecular characterization of castration-resistant prostate cancer (CRPC). These efforts hold promise for development of therapies that target alterations unique to an individual patient's prostate cancer. Targets include androgens and the androgen receptor pathway, pathways associated with hormone-resistant disease, and the immune system. In aggregate, this will allow physicians to choose treatments based on a particular tumor profile. As these approaches are developed, CRPC treatment is becoming an example of truly personalized medicine. C1 [Van Allen, Eliezer M.; Pomerantz, Mark] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Van Allen, Eliezer M.] Broad Inst Harvard & MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. RP Pomerantz, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM Mark_Pomerantz@dfci.harvard.edu OI Van Allen, Eliezer/0000-0002-0201-4444 NR 41 TC 4 Z9 4 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 2012 VL 39 IS 4 BP 483 EP + DI 10.1016/j.ucl.2012.07.005 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 047UK UT WOS:000311866800006 PM 23084525 ER PT J AU Morgans, AK Smith, MR AF Morgans, Alicia K. Smith, Matthew R. TI Bone-Targeted Agents Preventing Skeletal Complications in Prostate Cancer SO UROLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Prostate cancer; Skeletal complications; Bone; Side effects of therapy; Skeletal related events; ADT ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; ORAL SODIUM CLODRONATE; ADVANCED MULTIPLE-MYELOMA; PLACEBO-CONTROLLED TRIAL; LONG-TERM EFFICACY; DOUBLE-BLIND; ZOLEDRONIC ACID; MINERAL DENSITY; POSTMENOPAUSAL WOMEN AB In men, prostate cancer is the most common non-cutaneous malignancy and the second most common cause of cancer death. Skeletal complications occur at various points during the disease course, either due to bone metastases directly, or as an unintended consequence of androgen deprivation therapy (ADT). Bone metastases are associated with pathologic fractures, spinal cord compression, and bone pain and can require narcotics or palliative radiation for pain relief. ADT results in bone loss and fragility fractures. This review describes the biology of bone metastases, skeletal morbidity, and recent advances in bone-targeted therapies to prevent skeletal complications of prostate cancer. C1 [Morgans, Alicia K.; Smith, Matthew R.] Massachusetts Gen Hosp Canc Ctr, Dept Hematol Oncol, Boston, MA 02114 USA. RP Morgans, AK (reprint author), Massachusetts Gen Hosp Canc Ctr, Dept Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM alicia.morgans@vanderbilt.edu FU NCI NIH HHS [K24 CA121990] NR 72 TC 8 Z9 9 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0094-0143 J9 UROL CLIN N AM JI Urol. Clin. N. Am. PD NOV PY 2012 VL 39 IS 4 BP 533 EP + DI 10.1016/j.ucl.2012.07.009 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 047UK UT WOS:000311866800010 PM 23084529 ER PT J AU van Moorsel, CHM Christiani, DC AF van Moorsel, Coline H. M. Christiani, David C. TI Genetic Susceptibility to Sarcoidosis, a Chronic Inflammatory Disorder SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID GENOME-WIDE ASSOCIATION; LOCUS C1 [van Moorsel, Coline H. M.] St Antonius Hosp, Dept Pulmonol, Nieuwegein, Netherlands. [van Moorsel, Coline H. M.] Univ Med Ctr Utrecht, Div Heart & Lungs, Utrecht, Netherlands. [Christiani, David C.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP van Moorsel, CHM (reprint author), St Antonius Hosp, Dept Pulmonol, Nieuwegein, Netherlands. RI van Moorsel, Coline/E-9681-2010 NR 12 TC 3 Z9 3 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2012 VL 186 IS 9 BP 816 EP 818 DI 10.1164/rccm.201209-1582ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 037TB UT WOS:000311128300004 PM 23118080 ER PT J AU Ravnskov, U McCully, KS AF Ravnskov, Uffe McCully, Kilmer S. TI Infections May be Causal in the Pathogenesis of Atherosclerosis SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE Atherosclerosis; Cholesterol; Lipoproteins; Hypothesis; Infections; Microorganisms; Vulnerable plaque; Homocysteine ID ALL-CAUSE MORTALITY; ENDOTHELIAL DYSFUNCTION; MYCOPLASMA-PNEUMONIAE; MYOCARDIAL-INFARCTION; CHLAMYDIA-PNEUMONIAE; HIGH CHOLESTEROL; FOLLOW-UP; RISK; INFLAMMATION; LIPOPROTEIN AB There is a universal lack of exposure response between degree of lipid lowering and the outcome in clinical and angiographic trials questioning the current view on atherogenesis. However, there are numerous observations and experiments suggesting that microorganisms may play a causal role. A clue is the fact that the lipoproteins constitute an innate immune system by binding and inactivating microorganisms and their toxic products through formation of circulating complexes. Their size may increase in the presence of hyper-homocysteinemia because homocysteine reacts with low-density lipoprotein (LDL) to form homocysteinylated LDL aggregates. Autoantibodies against homocysteinylated or oxidized LDL may also enhance the aggregation. Because of the high extracapillary pressure, such aggregates may obstruct arterial vasa vasorum producing ischemia and cell death within the arterial wall leading to the creation of a vulnerable plaque. The many epidemiological observations, clinical findings and laboratory experiments that conflict with the cholesterol hypothesis are in good accordance with ours. C1 [McCully, Kilmer S.] VA Boston Healthcare Syst, Pathol & Lab Med Serv, W Roxbury, MA USA. [McCully, Kilmer S.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ravnskov, U (reprint author), Magle Stora Kyrkogata 9, S-22350 Lund, Sweden. EM ravnskov@tele2.se NR 33 TC 18 Z9 19 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD NOV PY 2012 VL 344 IS 5 BP 391 EP 394 DI 10.1097/MAJ.0b013e31824ba6e0 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 032WN UT WOS:000310750300008 PM 22495581 ER PT J AU Weil, AA Chowdhury, F Khan, AI Leung, DT Uddin, T Begum, YA Saha, NC Charles, RC LaRocque, RC Harris, JB Ryan, ET Qadri, F Calderwood, SB AF Weil, Ana A. Chowdhury, Fahima Khan, Ashraful I. Leung, Daniel T. Uddin, Taher Begum, Yasmin Ara Saha, Nirod Chandra Charles, Richelle C. LaRocque, Regina C. Harris, Jason B. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen B. TI Frequency of Reexposure to Vibrio cholerae O1 Evaluated by Subsequent Vibriocidal Titer Rise after an Episode of Severe Cholera in a Highly Endemic Area in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INFECTION-DERIVED IMMUNITY; RURAL EAST PAKISTAN; VACCINE FIELD-TRIAL; ANTIBODY TITRE; RESPONSES; SUSCEPTIBILITY; POPULATION; PREVALENCE; PROTECTION; PATHOGENS AB Vibriocidal antibody is a marker of recent exposure to Vibrio cholerae O1 infection. We examined vibriocidal titers for 1 year after an episode of severe cholera in patients in Dhaka, Bangladesh; 16 of 53 (30%) patients had a fourfold or greater increase in vibriocidal titer between 6 and 12 months after an episode of severe cholera, suggesting reexposure to the organism. Among patients with rises in titers during follow-up, the patients initially infected with serotype Ogawa had earlier rises in titer than the patients initially infected with serotype Inaba. These data and others suggest that an episode of severe cholera protects against symptomatic disease for several years, but reexposure to the organism occurs frequently in an endemic area, with immunological boosts beginning as early as 6 months after severe disease. Repeated exposures to V. cholerae in endemic areas may be a necessary component for long-lasting protection against severe disease. C1 [Charles, Richelle C.; LaRocque, Regina C.; Harris, Jason B.; Ryan, Edward T.; Calderwood, Stephen B.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02481 USA. [Chowdhury, Fahima; Khan, Ashraful I.; Leung, Daniel T.; Uddin, Taher; Begum, Yasmin Ara; Saha, Nirod Chandra; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Ctr Vaccine Sci, Dhaka 1000, Bangladesh. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02481 USA. EM aweil@partners.org; fchowdhury@icddrb.org; ashrafk@icddrb.org; dleung@partners.org; taher_imm@icddrb.org; yasmin@icddrb.org; nirod@icddrb.org; rccharles@partners.org; rclarocque@partners.org; jbharris@partners.org; etryan@partners.org; fqadri@icddrb.org; scalderwood@partners.org OI leung, daniel/0000-0001-8401-0801 FU Partners Healthcare Center of Expertise in Global and Humanitarian Health Travel Grant; Fogarty International Center [R24 TW007988]; American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund; Harvard Initiative for Global Health Post-Doctoral Fellowship in Global Infectious Diseases; Training Grant in Vaccine Development and Public Health [TW005572]; Career Development Awards [K08 AI089721, K01 TW07144, K01 TW07409]; Howard Hughes Medical Institute; National Institutes of Health [U01 AI077883, AI058935, R03 AI063079]; Swedish Agency for International Development and Cooperation; American Recovery and Reinvestment Act (ARRA) Post-Doctoral Fellowship in Global Infectious Diseases [TW05572] FX This work was supported by a Partners Healthcare Center of Expertise in Global and Humanitarian Health Travel Grant (to A.A.W.); Fogarty International Clinical Research Scholars Award R24 TW007988 (to F.C. and A.I.K.) from the Fogarty International Center; American Recovery and Reinvestment Act (ARRA) Post-Doctoral Fellowship in Global Infectious Diseases TW05572 (to D.T.L.); a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine and Hygiene-Burroughs Wellcome Fund (to D.T.L.); the Harvard Initiative for Global Health Post-Doctoral Fellowship in Global Infectious Diseases (to D.T.L); a Training Grant in Vaccine Development and Public Health TW005572 (to T.U., E.T.R., and F.Q.); Career Development Awards K08 AI089721 (to R.C.C.), K01 TW07144 (to R.C.L.), and K01 TW07409 (to J.B.H.); a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (to R.C.L.); National Institutes of Health Grants U01 AI077883 (to E.T.R.), AI058935 (to E.T.R. and S.B.C.), and R03 AI063079 (to F.Q.); and the Swedish Agency for International Development and Cooperation (F.Q.). NR 30 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2012 VL 87 IS 5 BP 921 EP 926 DI 10.4269/ajtmh.2012.12-0323 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 036VI UT WOS:000311060000021 PM 22964723 ER PT J AU Bartnikas, LM Sheehan, WJ Hoffman, EB Permaul, P Dioun, AF Friedlander, J Baxi, SN Schneider, LC Phipatanakul, W AF Bartnikas, Lisa M. Sheehan, William J. Hoffman, Elaine B. Permaul, Perdita Dioun, Anahita F. Friedlander, James Baxi, Sachin N. Schneider, Lynda C. Phipatanakul, Wanda TI Predicting food challenge outcomes for baked milk: role of specific IgE and skin prick testing SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ALLERGY; CHILDREN; TOLERANCE; ALLERGENICITY; RESOLUTION; PROTEIN; MATRIX; EGG AB Background: Cow's milk allergy is the most common food allergy in childhood. Many children with IgE-mediated cow's milk allergy may tolerate baked milk products, but few data exist on predictors of outcomes of baked milk challenges. Objective: To determine the relation of milk protein allergen specific IgE (sIgE) levels and skin prick test (SPT) wheal size with baked milk challenge outcomes. Methods: A retrospective medical record review was conducted of 35 baked milk challenges. SPT results, sIgE levels, demographic characteristics, and food challenge results were analyzed. Results: Thirty-five children underwent open challenges to baked milk and 29 (83%) passed. Of those who failed, 3 (50%) passed the initial clinic challenge but developed symptoms to ongoing exposure at home, days to months later. One child who ultimately failed at home required epinephrine. Compared with those who passed, children who failed were younger (median age, 8.9 and 3.7 years, respectively; P=.02). Children with a milk SPT wheal less than 12mm were more than 90% likely to pass a baked milk challenge, and no child with a milk SPT wheal less than 7mm failed a baked milk challenge. We were also able to establish more than 90% predictive values for passing baked milk challenges with a casein SPT wheal of 9 mm, a milk sIgE level of 1.0 kU/L, and a casein sIgE level of 0.9 kU/L. Conclusion: Most children allergic to cow's milk tolerated baked milk. Milk protein SPT wheal may be more reliable than sIgE level in predicting outcomes of baked milk challenges. It is important to be aware of the possibility of late reactions to ongoing baked milk exposure. (C) 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Phipatanakul, Wanda] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Bartnikas, Lisa M.; Sheehan, William J.; Permaul, Perdita; Dioun, Anahita F.; Friedlander, James; Baxi, Sachin N.; Schneider, Lynda C.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston, MA USA. [Hoffman, Elaine B.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Pulm Allergy & Immunol, Boston, MA 02114 USA. RP Phipatanakul, W (reprint author), Boston Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU American Academy of Allergy, Asthma, and Immunology/Food Allergy Initiative Howard Gittis Memorial Third/Fourth Year Fellowship/Junior Faculty Research Award; National Institutes of Health [R01 AI 073964] FX Dr Bartnikas is supported by the 2010 American Academy of Allergy, Asthma, and Immunology/Food Allergy Initiative Howard Gittis Memorial Third/Fourth Year Fellowship/Junior Faculty Research Award. This research is supported by grant R01 AI 073964 from the National Institutes of Health (PI, Dr. Phipatanakul). NR 19 TC 21 Z9 22 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2012 VL 109 IS 5 BP 309 EP + DI 10.1016/j.anai.2012.07.026 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 041VK UT WOS:000311429100007 PM 23062384 ER PT J AU Mullins, RJ Clark, S Wiley, V Eyles, D Camargo, CA AF Mullins, Raymond James Clark, Sunday Wiley, Veronica Eyles, Darryl Camargo, Carlos A., Jr. TI Neonatal vitamin D status and childhood peanut allergy: a pilot study SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID FOOD ALLERGY; UNITED-STATES; 25-HYDROXYVITAMIN D; REGIONAL-VARIATION; D SUPPLEMENTATION; ANAPHYLAXIS; PRESCRIPTIONS; SENSITIZATION; AUSTRALIA; PREGNANCY AB Background: Although a number of factors have been proposed to explain the increase in food allergy during the last decade, the possibility that vitamin D status may play a pathogenic role has received recent attention. Objective: To determine whether lower levels of neonatal 25-hydroxyvitamin D (25[OH] D) would be observed in children with peanut allergy compared with in population controls. Methods: The concentration of 25(OH) D was measured from neonatal dried blood samples by liquid chromatography tandem mass spectrometry. Levels were compared between children with IgE-mediated peanut allergy younger than 72 months assessed during 2008-2011 in a specialist referral clinic in the Australian Capital Territory and population births matched by sex, birth date, and birth location. Odds ratios were calculated for the matched pairs across quintiles of 25(OH) D. Results: Neonatal 25(OH) D levels ranged from 8 to 180 nmol/L (median, 66 nmol/L; interquartile range, 46-93 nmol/L); only 4 children (3%) had levels less than 25 nmol/L, and 24 (20.9%) had levels greater than 100 nmol/L. No significant association was found between socioeconomic or clinical factors and 25(OH) D levels. Compared with the reference group (50-74.9 nmol/L), levels of 75 to 99.9 nmol/L were associated with lower risk of peanut allergy (P=.02). No further reduction was found at levels of 100 nmol/L or higher, and the risk of peanut allergy at levels less than 50 nmol/L was not significantly different from the reference group. Conclusion: The relationship between neonatal 25(OH) D level and childhood peanut allergy was nonlinear, with slightly higher levels (75-99.9 nmol/L) associated with lower risk than those in the reference group (50-74.9 nmol/L). Vitamin D status may be one of many potential factors contributing to childhood peanut allergy pathogenesis. (C) 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved. C1 [Mullins, Raymond James] John James Med Ctr, Deakin, ACT 2600, Australia. [Mullins, Raymond James] Sch Med, Canberra, ACT, Australia. [Mullins, Raymond James] Australian Natl Univ, Canberra, ACT, Australia. [Mullins, Raymond James] Univ Canberra, Fac Hlth, Dept Clin Immunol, Canberra, ACT 2601, Australia. [Clark, Sunday] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA. [Wiley, Veronica] Childrens Hosp Westmead, New S Wales Newborn Screening Program, Westmead, NSW, Australia. [Wiley, Veronica] Univ Sydney, Dept Med Genet, Sydney, NSW 2006, Australia. [Wiley, Veronica] Univ Sydney, Dept Pediat & Child Hlth, Sydney, NSW 2006, Australia. [Eyles, Darryl] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Mullins, RJ (reprint author), John James Med Ctr, Suite 1,175 Strickland Crescent, Deakin, ACT 2600, Australia. EM rmullins@allergycapital.com.au OI Mullins, Raymond/0000-0002-0267-1591 FU Commonwealth Serum Laboratories Australia; Alphapharm Australia; Abbott Nutrition Australia; Ilhan Food Allergy Foundation; Dey (Basking Ridge, New Jersey); Sanofi-Aventis (Bridgewater, New Jersey) FX Dr Mullins has received unrestricted investigator-initiated grants from Commonwealth Serum Laboratories Australia and Alphapharm Australia (the past and current Australian distributors of EpiPen), Abbott Nutrition Australia, and the Ilhan Food Allergy Foundation within the last 5 years. Dr Camargo has received investigator-initiated research grants from and consulted for Dey (Basking Ridge, New Jersey) and Sanofi-Aventis (Bridgewater, New Jersey). The other authors report no conflict of interest. NR 42 TC 8 Z9 9 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 EI 1534-4436 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2012 VL 109 IS 5 BP 324 EP 328 DI 10.1016/j.anai.2012.07.009 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 041VK UT WOS:000311429100010 PM 23062387 ER PT J AU Friedman, AD Kobler, JB Landau-Zemer, T Barbu, AM Burns, JA AF Friedman, Aaron D. Kobler, James B. Landau-Zemer, Tali Barbu, Anca M. Burns, James A. TI High-Force Simulated Intubation Fails to Dislocate Cricoarytenoid Joint in Ex Vivo Human Larynges SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 18-19, 2012 CL San Diego, CA SP Amer Broncho Esophagol Assoc DE arytenoid cartilage; dislocation; injury; intubation; vocal cord paralysis; voice disorder; wound ID ARYTENOID DISLOCATION; COMPUTED-TOMOGRAPHY; SUBLUXATION; ANESTHESIA AB Objectives: We assessed the likelihood of arytenoid dislocation during intubation through the application of controlled force. Methods: Six cadaveric human larynges were mounted in an apparatus for simulating forcible collision with the arytenoid complexes. An endotracheal tube tip probe (ETTP) was Used to push one arytenoid complex, and a non-slip probe (NSP) was tested on the other. Increasing pressure was applied until the probes either slipped or reached 5 kg of force. Dissection was then performed to assess the integrity of the cricoarytenoid ligament. The forces obtained by pushing an endotracheal tube against an electronic balance were measured to estimate the maximal possible intubating force. Results: None of the ETTP or NSP trials disrupted the cricoarytenoid joint ligaments, and the joint never appeared to be dislocated. The mean maximal forces were 1.8 kg for the ETTP (after which, slippage consistently occurred) and 4.7 kg for the NSP. The mean maximal forces from an endotracheal tube pushed against a scale were 1.5 kg (without stylet) and 4.6 kg (with stylet). Conclusions: Arytenoid dislocation did not happen, and gross disruption of the joint capsule or ligament did not occur, even when the testing approximated the maximum force achievable under extreme conditions. Endotracheal tube insertion thus seems unlikely to cause arytenoid dislocation. C1 [Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. NR 17 TC 2 Z9 2 U1 1 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 2012 VL 121 IS 11 BP 746 EP 753 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 042JR UT WOS:000311468000008 PM 23193908 ER PT J AU Maturo, S Benboujja, F Boudoux, C Hartnick, C AF Maturo, Stephen Benboujja, Fouzi Boudoux, Caroline Hartnick, Christopher TI Quantitative Distinction of Unique Vocal Fold Subepithelial Architectures Using Optical Coherence Tomography SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Broncho-Esophagological-Association CY APR 18-19, 2012 CL San Diego, CA SP Amer Broncho Esophagol Assoc DE development; maturation; pediatrics; vocal fold ID LAMINA PROPRIA; AIRWAY AB Objectives: The primary objective of this study was to quantitatively analyze ex vivo porcine, fetal human, and adult human vocal folds by use of optical coherence tomography (OCT). A secondary objective was to quantitatively discriminate among 1-, 2-, and 3-layer lamina propria structures. Methods: We performed an analysis of the vocal folds of 10 adult pig, 3 adult human, and 2 fetal human vocal fold specimens using OCT and histologic techniques. We present a quantitative comparison of the OCT results and histologic findings. Results: We found that OCT allowed for the visualization of the subepithelial vocal fold architecture of all imaged tissue, and that it revealed distinct characteristic signal intensities for each type of specimen. Conclusions: Optical coherence tomography was developed for in vivo imaging of biological microstructures. This study demonstrates the ability of OCT to differentiate between the vocal fold architectures of 3 histologically distinct types of vocal folds. Future studies aim to develop a quantitative optical imaging algorithm that can be used to facilitate an in vivo longitudinal clinical investigation of the changes that occur in this layered structure over time and maturation. C1 [Maturo, Stephen; Benboujja, Fouzi; Boudoux, Caroline; Hartnick, Christopher] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Hartnick, C (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 15 TC 7 Z9 7 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 2012 VL 121 IS 11 BP 754 EP 760 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 042JR UT WOS:000311468000009 PM 23193909 ER PT J AU Baker, LD Barsness, SM Borson, S Merriam, GR Friedman, SD Craft, S Vitiello, MV AF Baker, Laura D. Barsness, Suzanne M. Borson, Soo Merriam, George R. Friedman, Seth D. Craft, Suzanne Vitiello, Michael V. TI Effects of Growth Hormone-Releasing Hormone on Cognitive Function in Adults With Mild Cognitive Impairment and Healthy Older Adults Results of a Controlled Trial SO ARCHIVES OF NEUROLOGY LA English DT Article ID FACTOR-I; ALZHEIMERS-DISEASE; INSULIN-RESISTANCE; CEREBROSPINAL-FLUID; VASCULAR DEMENTIA; AEROBIC EXERCISE; IGF-1 RESISTANCE; BODY-COMPOSITION; APOLIPOPROTEIN-E; WORKING-MEMORY AB Background: Growth hormone-releasing hormone (GHRH), growth hormone, and insulin-like growth factor 1 have potent effects on brain function, their levels decrease with advancing age, and they likely play a role in the pathogenesis of Alzheimer disease. Previously, we reported favorable cognitive effects of short-term GHRH administration in healthy older adults and provided preliminary evidence to suggest a similar benefit in adults with mild cognitive impairment (MCI). Objective: To examine the effects of GHRH on cognitive function in healthy older adults and in adults with MCI. Design: Randomized, double-blind, placebo-controlled-trial. Setting: Clinical Research Center, University of Washington School of Medicine in Seattle. Participants: A total of 152 adults (66 with MCI) ranging in age from 55 to 87 years (mean age, 68 years); 137 adults (76 healthy participants and 61 participants with MCI) successfully completed the study. Intervention: Participants self-administered daily subcutaneous injections of tesamorelin (Theratechnologies Inc), a stabilized analog of human GHRH (1 mg/d), or placebo 30 minutes before bedtime for 20 weeks. At baseline, at weeks 10 and 20 of treatment, and after a 10-week washout (week 30), blood samples were collected, and parallel versions of a cognitive battery were administered. Before and after the 20-week intervention, participants completed an oral glucose tolerance test and a dual-energy x-ray absorptiometry scan to measure body composition. Main Outcome Measures: Primary cognitive outcomes were analyzed using analysis of variance and included 3 composites reflecting executive function, verbal memory, and visual memory. Executive function was assessed with Stroop Color-Word Interference, Task Switching, the Self-Ordered Pointing Test, and Word Fluency, verbal memory was assessed with Story Recall and the Hopkins Verbal Learning Test, and visual memory was assessed with the Visual-Spatial Learning Test and Delayed Match-to-Sample. Results: The intent-to-treat analysis indicated a favorable effect of GHRH on cognition (P=.03), which was comparable in adults with MCI and healthy older adults. The completer analysis showed a similar pattern, with a more robust GHRH effect (P=.002). Subsequent analyses indicated a positive GHRH effect on executive function (P=.005) and a trend showing a similar treatment-related benefit in verbal memory(P=.08). Treatment with GHRH increased insulinlike growth factor 1 levels by 117% (P<.001), which remained within the physiological range, and reduced percent body fat by 7.4% (P<.001). Treatment with GHRH increased fasting insulin levels within the normal range by 35% in adults with MCI (P<.001) but not in healthy adults. Adverse events were mild and were reported by 68% of GHRH treated adults and 36% of those who received placebo. Conclusions: Twenty weeks of GHRH administration had favorable effects on cognition in both adults with MCI and healthy older adults. Longer-duration treatment trials are needed to further examine the therapeutic potential of GHRH administration on brain health during normal aging and "pathological aging." C1 [Baker, Laura D.; Craft, Suzanne] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Merriam, George R.] Vet Affairs Puget Sound Hlth Care Syst, Res & Dev, Seattle, WA 98108 USA. [Baker, Laura D.; Borson, Soo; Craft, Suzanne; Vitiello, Michael V.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Merriam, George R.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Baker, LD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, GRECC S182,1660 S Columbian Way, Seattle, WA 98108 USA. EM ldbaker@uw.edu OI Vitiello, Michael/0000-0002-9776-0473 FU National Institutes of Health/National Institute of Aging [AG025515, AG030484]; US Department of Veterans Affairs; National Institutes of Health/National Center for Research Resources [ULRR025014] FX This research was supported by National Institutes of Health/National Institute of Aging grants AG025515 (to Dr Vitiello) and AG030484 (to Dr Friedman) and by the US Department of Veterans Affairs. A portion of this work was conducted through the Clinical Research Center Facility at the University of Washington Medical Center, which is supported by the National Institutes of Health/National Center for Research Resources grant ULRR025014. NR 80 TC 34 Z9 35 U1 2 U2 50 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2012 VL 69 IS 11 BP 1420 EP 1429 DI 10.1001/archneurol.2012.1970 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 035XT UT WOS:000310987500003 PM 22869065 ER PT J AU Duran-Struuck, R Matar, A Crepeau, R Gusha, A Schenk, M Hanekamp, I Pathiraja, V Spitzer, TR Sachs, DH Huang, CA AF Duran-Struuck, Raimon Matar, Abraham Crepeau, Rebecca Gusha, Ashley Schenk, Marian Hanekamp, Isabel Pathiraja, Vimukthi Spitzer, Thomas R. Sachs, David H. Huang, Christene A. TI Lack of Antidonor Alloantibody Does Not Indicate Lack of Immune Sensitization: Studies of Graft Loss in a Haploidentical Hematopoietic Cell Transplantation Swine Model SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation ID LARGE-ANIMAL-MODEL; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; MIXED CHIMERISM; T-CELLS; TOLERANCE; FAILURE; ENGRAFTMENT; RECIPIENTS; RISK AB Loss of chimerism is an undesirable outcome of allogeneic hematopoietic cell transplantation (HCT) after reduced-intensity conditioning. Understanding the nature of cellular and humoral immune responses to HCT after graft loss could lead to improved retransplantation strategies. We investigated the immunologic responses after graft loss in miniature swine recipients of haploidentical HCT that received reduced-intensity conditioning. After the loss of peripheral blood chimerism, antidonor cellular responses were present without detectable antidonor antibody. Reexposure to donor hematopoietic cells after graft loss induced a sensitized antidonor cellular response. No induced antidonor antibody response could be detected despite evidence of cellular sensitization to donor cells. In contrast, unconditioned animals exposed repeatedly to similar doses of haploidentical donor cells developed antidonor antibody responses. These results could have important implications for the design of treatment strategies to overcome antidonor responses in HCT and improve the outcome of retransplantation after graft loss. Biol Blood Marrow Transplant 18: 1629-1637 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Duran-Struuck, Raimon; Matar, Abraham; Crepeau, Rebecca; Gusha, Ashley; Schenk, Marian; Hanekamp, Isabel; Pathiraja, Vimukthi; Sachs, David H.; Huang, Christene A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02129 USA. [Spitzer, Thomas R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med, Boston, MA 02129 USA. RP Duran-Struuck, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 149 13th St, Boston, MA 02129 USA. EM rduranst@gmail.com FU National Center for Research Resources [K01RR024466, R01AI084657, P01CA111519] FX This research was supported by National Center for Research Resources Grants K01RR024466 (to R.D.S.), R01AI084657, and P01CA111519. The authors have no conflicts of interest to disclose. NR 31 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2012 VL 18 IS 11 BP 1629 EP 1637 DI 10.1016/j.bbmt.2012.08.004 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 029KF UT WOS:000310493700004 PM 22892552 ER PT J AU Hill, JA Koo, S Suarez, BBG Ho, VT Cutler, C Koreth, J Armand, P Alyea, EP Baden, LR Antin, JH Soiffer, RJ Marty, FM AF Hill, Joshua A. Koo, Sophia Suarez, Belisa B. Guzman Ho, Vincent T. Cutler, Corey Koreth, John Armand, Philippe Alyea, Edwin P., III Baden, Lindsey R. Antin, Joseph H. Soiffer, Robert J. Marty, Francisco M. TI Cord-Blood Hematopoietic Stem Cell Transplant Confers an Increased Risk for Human Herpesvirus-6-Associated Acute Limbic Encephalitis: A Cohort Analysis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Herpes; HHV-6; Transplantation; Cord; Encephalitis ID BONE-MARROW TRANSPLANT; HERPESVIRUS 6 ENCEPHALITIS; POLYMERASE-CHAIN-REACTION; HOST-DISEASE PROPHYLAXIS; HHV-6 VIRAL LOAD; HUMAN-HERPESVIRUS-6 INFECTION; CLINICAL-FEATURES; VARIANT-B; CEREBROSPINAL-FLUID; PREEMPTIVE THERAPY AB Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute limbic encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating limbic encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days (P < .001), respectively. Risk factors for HHV-6-PALE on multivariable Cox modeling were UCBT (adjusted hazard ratio [aHR], 20.0; 95% confidence interval [CI], 7.3-55.0; P < .001), time-dependent acute graft-versus-host disease (aGVHD) grades II to IV (aHR, 7.5; 95% CI, 2.8-19.8; P <.001), and adult-mismatched donor (aHR, 4.3; 95% CI, 1.1-17.3; P =.04). Death from HHV-6-PALE occurred in 50% of affected patients undergoing UCBT and no recipients of adult-donor cells. Patients receiving UCBT have increased risk for HHV-6-PALE and greater morbidity from this disease. Biol Blood Marrow Transplant 18: 1638-1648 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Koo, Sophia; Suarez, Belisa B. Guzman; Baden, Lindsey R.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hill, Joshua A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ho, Vincent T.; Cutler, Corey; Koreth, John; Armand, Philippe; Alyea, Edwin P., III; Antin, Joseph H.; Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. EM fmarty@partners.org OI HILL, JOSHUA/0000-0002-7665-7100 FU Jock and Bunny Adams Research and Education Endowment, NIH [CA142106]; Astellas Pharma US; Chimerix FX The Jock and Bunny Adams Research and Education Endowment, NIH grant CA142106. Francisco M. Marty has received research grant support from Astellas Pharma US and Chimerix for unrelated work. All other authors declare no potential financial interest. NR 59 TC 26 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2012 VL 18 IS 11 BP 1638 EP 1648 DI 10.1016/j.bbmt.2012.04.016 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 029KF UT WOS:000310493700005 PM 22564265 ER PT J AU Palmer, JM Lee, SJ Chai, XY Storer, BE Flowers, MED Schultz, KR Inamoto, Y Cutler, C Pidala, J Arora, M Jacobsohn, DA Carpenter, PA Pavletic, SZ Martin, PJ AF Palmer, Jeanne M. Lee, Stephanie J. Chai, Xiaoyu Storer, Barry E. Flowers, Mary E. D. Schultz, Kirk R. Inamoto, Yoshihiro Cutler, Corey Pidala, Joseph Arora, Mukta Jacobsohn, David A. Carpenter, Paul A. Pavletic, Steven Z. Martin, Paul J. TI Poor Agreement between Clinician Response Ratings and Calculated Response Measures in Patients with Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic hematopoietic cell transplantation; Chronic graft-versus-host disease; Response assessment ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; THERAPEUTIC RESPONSE; CHRONIC GVHD; PHASE-II; CRITERIA; RELIABILITY; TRIALS AB In 2005, a National Institutes of Health consensus conference was held to refine methods for research in patients with chronic graft-versus-host disease, including proposed objective response measures and a provisional algorithm for calculating organ-specific and overall response. In this study, we used weighted kappa statistics to evaluate the level of agreement between clinician response ratings and calculated response categories in patients with chronic graft-versus-host disease. The study included 290 patients who had paired enrollment and follow-up visits. Based on a set of objective measures, 37% of the patients had an overall complete or partial response, whereas clinicians reported an overall complete or partial response rate of 71% (slight to fair agreement, weighted kappa 0.20). Agreement rates between calculated organ-specific responses and clinician-reported changes in skin, mouth, and eyes were fair to moderate (weighted kappa, 0.28-0.54). We conclude that for both overall and organ-specific comparisons, clinician response ratings did not agree well with calculated response categories. Possible reasons for this discrepancy include a high clinical sensitivity for detecting response, a clinical predisposition to recognize selective improvements as overall response, the large change in objective measures proposed to define response, and the high incidence of progressive disease based on new manifestations. Conclusions from prior literature reporting high overall response rates based on clinician judgment would not be supported if the provisional algorithm had been applied to calculate response. Our analysis also highlights the need to define an overall response measure that incorporates both patient-reported and objective measures and accurately reflects the outcome in patients with a mixed response in which one organ or site improves, whereas another shows new involvement. Biol Blood Marrow Transplant 18: 1649-1655 (2012) (C) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Palmer, Jeanne M.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Lee, Stephanie J.; Chai, Xiaoyu; Storer, Barry E.; Flowers, Mary E. D.; Inamoto, Yoshihiro; Carpenter, Paul A.; Martin, Paul J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Schultz, Kirk R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Arora, Mukta] Univ Minnesota, Minneapolis, MN USA. [Jacobsohn, David A.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. RP Palmer, JM (reprint author), Med Coll Wisconsin, Div Hematol & Oncol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM sjlee@fhcrc.org FU NIH/NCI [CA 118953] FX This work was supported by grant CA 118953 (PI: Lee, SJ) NIH/NCI. NR 21 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2012 VL 18 IS 11 BP 1649 EP 1655 DI 10.1016/j.bbmt.2012.05.005 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 029KF UT WOS:000310493700006 PM 22691695 ER PT J AU Cutler, C Ballen, KK AF Cutler, Corey Ballen, Karen K. TI Improving outcomes in umbilical cord blood transplantation: State of the art SO BLOOD REVIEWS LA English DT Review DE Umbilical cord blood; Transplantation ID STEM-CELL TRANSPLANTATION; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW; ACUTE-LEUKEMIA; MODULATES DIFFERENTIATION; RETROSPECTIVE ANALYSIS; CD34(+) CELLS; SELF-RENEWAL; HLA; ADULTS AB Only 30% of patients who require an allogeneic hematopoietic cell transplant will have a HLA matched sibling donor. Many patients, particularly those patients with diverse racial and ethnic backgrounds, may not be able to identify a suitably matched unrelated donor. Over 25,000 umbilical cord blood transplant procedures have been performed in the last 25 years. Considerable challenges exist in defining the appropriate conditioning regimen and graft vs host disease prophylaxis, surmounting issues of cell dose and delayed engraftment, and improving immune recovery. In this review, we discuss strategies to improve umbilical cord blood transplant outcomes, focusing on cord blood unit selection, expansion, and homing efficiency. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02114 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, 0 Emerson,Suite 118, Boston, MA 02114 USA. EM kballen@partners.org NR 62 TC 16 Z9 16 U1 2 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD NOV PY 2012 VL 26 IS 6 BP 241 EP 246 DI 10.1016/j.blre.2012.08.001 PG 6 WC Hematology SC Hematology GA 042IZ UT WOS:000311466200002 PM 22958984 ER PT J AU Gong, J Hutter, C Baron, JA Berndt, S Caan, B Campbell, PT Casey, G Chan, AT Cotterchio, M Fuchs, CS Gallinger, S Giovannucci, E Harrison, T Hayes, R Hsu, L Jiao, S Lin, Y Lindor, NM Newcomb, P Pflugeisen, B Phipps, AI Rohan, T Schoen, R Seminara, D Slattery, ML Stelling, D Thomas, F Warnick, G White, E Potter, J Peters, U AF Gong, Jian Hutter, Carolyn Baron, John A. Berndt, Sonja Caan, Bette Campbell, Peter T. Casey, Graham Chan, Andrew T. Cotterchio, Michelle Fuchs, Charles S. Gallinger, Steven Giovannucci, Edward Harrison, Tabitha Hayes, Richard Hsu, Li Jiao, Shuo Lin, Yi Lindor, Noralane M. Newcomb, Polly Pflugeisen, Bethann Phipps, Amanda I. Rohan, Thomas Schoen, Robert Seminara, Daniela Slattery, Martha L. Stelling, Deanna Thomas, Fridtjof Warnick, Greg White, Emily Potter, John Peters, Ulrike TI A Pooled Analysis of Smoking and Colorectal Cancer: Timing of Exposure and Interactions with Environmental Factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; COLON-CANCER; UNITED-STATES; TOBACCO USE; RESPONSE RELATIONSHIPS; ALCOHOL-CONSUMPTION; PROSPECTIVE COHORT; LUNG-CANCER; FOLLOW-UP; RISK AB Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association. Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors. Results: Current smokers [OR, 1.26; 95% confidence interval (Cl), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04). Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking. Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology. Cancer Epidemiol Biomarkers Prev; 21(11); 1974-85. (C)2012 AACR. C1 [Gong, Jian; Hutter, Carolyn; Harrison, Tabitha; Hsu, Li; Jiao, Shuo; Lin, Yi; Newcomb, Polly; Pflugeisen, Bethann; Phipps, Amanda I.; Stelling, Deanna; Warnick, Greg; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Hutter, Carolyn; Newcomb, Polly; Phipps, Amanda I.; White, Emily; Potter, John; Peters, Ulrike] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98109 USA. [Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98109 USA. [Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Seminara, Daniela] NCI, Epidemiol & Genet Res Program, Bethesda, MD 20892 USA. [Caan, Bette] Kaiser Permanente, Div Res, Med Care Program, Oakland, CA USA. [Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [Casey, Graham] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Cotterchio, Michelle] Canc Care Ontario, Populat Studies & Surveillance, Toronto, ON, Canada. [Gallinger, Steven] Toronto Gen Hosp, Div Gen Surg, Univ Hlth Network, Toronto, ON, Canada. [Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [Baron, John A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. [Thomas, Fridtjof] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Hayes, Richard] NYU, Dept Environm Med, Div Epidemiol, Sch Med, New York, NY 10016 USA. [Schoen, Robert] Univ Pittsburgh, Dept Epidemiol, Med Ctr, Pittsburgh, PA 15261 USA. [Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA. [Rohan, Thomas] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Potter, John] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Lindor, Noralane M.] Mayo Clin, Dept Med Genet, Rochester, MN USA. RP Peters, U (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM upeters@fhcrc.org RI Gallinger, Steven/E-4575-2013; OI Potter, John/0000-0001-5439-1500 FU National Cancer Institute, NIH under RFA [CA-95-011]; Australasian Colorectal Cancer Family Registry [U01 CA097735]; Mayo Clinic Cooperative Family Registry for Colon Cancer Studies [U01 CA074800]; Seattle Colorectal Cancer Family Registry [U01 CA074794]; Ontario Registry for Studies of Familial Colorectal Cancer [U01 CA074783]; Ontario Research Fund; Canadian Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute; NIH [P01 CA 055075, R01 137178, P50 CA 127003]; Intramural Research Program of the Division of Cancer Epidemiology and Genetics; Division of Cancer Prevention, National Cancer Institute, U.S. Department of Health and Human Services; Intramural Research Program of the National Cancer Institute; NIH from the National Cancer Institute and Office of Dietary Supplements [K05 CA154337]; National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX CCFR was supported by the National Cancer Institute, NIH under RFA # CA-95-011 and through cooperative agreements with members of the Colon Cancer Family Registry and P.I.s.; The following Colon CFR centers contributed data to the manuscript and were supported by the following sources: Australasian Colorectal Cancer Family Registry (U01 CA097735), Mayo Clinic Cooperative Family Registry for Colon Cancer Studies (U01 CA074800), Seattle Colorectal Cancer Family Registry (U01 CA074794), and the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783). The OFCCR was also supported by a GL2 grant from the Ontario Research Fund, the Canadian Institutes of Health Research, and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian Cancer Society Research Institute.; HPFS is supported by the NIH (P01 CA 055075, R01 137178, and P50 CA 127003).; PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, U.S. Department of Health and Human Services. Control samples were derived from the PLCO Screening Trial, which was supported by the Intramural Research Program of the National Cancer Institute.; VITAL is supported in part by the NIH (K05 CA154337) from the National Cancer Institute and Office of Dietary Supplements.; The WHI program is funded by the National Heart, Lung, and Blood Institute, NIH, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 61 TC 18 Z9 18 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2012 VL 21 IS 11 BP 1974 EP 1985 DI 10.1158/1055-9965.EPI-12-0692 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 035GP UT WOS:000310931700010 PM 23001243 ER PT J AU Parikh, NI Honeycutt, EF Roe, MT Neely, M Rosenthal, EJ Mittleman, MA Carrozza, JP Ho, KKL AF Parikh, Nisha I. Honeycutt, Emily F. Roe, Matthew T. Neely, Megan Rosenthal, Eric J. Mittleman, Murray A. Carrozza, Joseph P., Jr. Ho, Kalon K. L. TI Left and Codominant Coronary Artery Circulations Are Associated With Higher In-Hospital Mortality Among Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndromes Report From the National Cardiovascular Database Cath Percutaneous Coronary Intervention (CathPCI) Registry SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE coronary dominance; left dominance; acute coronary syndrome; risk stratification; mortality ID RISK PREDICTION; DOMINANCE AB Background-Left or codominant coronary arterial circulation may represent less well-balanced myocardial perfusion and thus confer worse prognosis in acute coronary syndrome, especially for culprit lesions arising from the left coronary artery. Methods and Results-We related left and codominance, relative to right dominance, with in-hospital mortality in 207 926 percutaneous coronary interventions (PCI) for acute coronary syndromes from July 1, 2009 through June 30, 2010 in the National Cardiovascular Data Registry Cath Percutaneous Coronary Intervention (CathPCI) Registry database version 4. Generalized estimating equations and logistic regression analyses were used in unadjusted and multivariable adjusted models. Models were adjusted using the validated National Cardiovascular Data Registry mortality risk model. We performed subgroup analyses and formally tested for effect modification by the epicardial coronary artery containing the culprit lesion. Left coronary dominance was associated with higher in-hospital mortality in unadjusted (odds ratio=1.29, 95% confidence interval [CI], 1.17-1.42) and adjusted models (1.19, 95% CI, 1.06-1.34). Codominance was associated with worsened mortality only in adjusted models (odds ratio=1.16, 95% CI, 1.01-1.34). Addition of coronary dominance to the National Cardiovascular Data Registry risk model did not materially change model discrimination or calibration. The odds of death for left versus right dominance among those with left circumflex or left main culprit lesions was 1.25 (95% CI, 1.02-1.53), for right coronary artery lesions was 1.19 (95% CI, 0.83-1.71), and for left anterior descending artery lesions was 1.09 (95% CI, 0.93-1.28). There was no statistical evidence for effect modification by culprit lesion vessel (P=0.8). Conclusions-Left and codominance are associated with modestly increased post-percutaneous coronary intervention in-hospital mortality in patients with acute coronary syndrome. Confirmation of these findings with angiographic core laboratory verification of coronary dominance and longer term follow-up will be desirable. (Circ Cardiovasc Qual Outcomes. 2012;5:775-782.) C1 [Parikh, Nisha I.] Queens Med Ctr, Div Cardiol, Honolulu, HI 96813 USA. [Parikh, Nisha I.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. [Honeycutt, Emily F.; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. [Neely, Megan] Duke Univ, Sch Med, Dept Biostat & Bioinformat, Durham, NC USA. [Roe, Matthew T.; Neely, Megan] Duke Univ, Sch Med, Dept Med, Durham, NC USA. [Rosenthal, Eric J.; Mittleman, Murray A.; Ho, Kalon K. L.] Harvard Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA USA. [Carrozza, Joseph P., Jr.] Tufts St Elizabeths Med Ctr, Div Cardiovasc, Boston, MA USA. RP Parikh, NI (reprint author), Queens Med Ctr, Div Cardiovasc, 1301 Punchbowl St, Honolulu, HI 96813 USA. EM nparikh@queens.org NR 11 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7705 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD NOV PY 2012 VL 5 IS 6 BP 775 EP 782 DI 10.1161/CIRCOUTCOMES.111.964593 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 041NZ UT WOS:000311409800013 PM 23110791 ER PT J AU Molnar, AO Parikh, CR Sint, K Coca, SG Koyner, J Patel, UD Butrymowicz, I Shlipak, M Garg, AX AF Molnar, Amber O. Parikh, Chirag R. Sint, Kyaw Coca, Steven G. Koyner, Jay Patel, Uptal D. Butrymowicz, Isabel Shlipak, Michael Garg, Amit X. TI Association of Postoperative Proteinuria with AKI after Cardiac Surgery among Patients at High Risk SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE KIDNEY INJURY; ACUTE-RENAL-FAILURE; GLOMERULAR-FILTRATION-RATE; DISEASE; MORTALITY; OUTCOMES; ALBUMINURIA; BIOMARKERS; DEATH; MICROALBUMINURIA AB Background and objectives Preoperative proteinuria is associated with a higher incidence of postoperative AM. Whether the same is true for postoperative proteinuria is uncertain. This study tested the hypothesis that increased proteinuria after cardiac surgery is associated with an increased risk for AKI. Design, setting, participants, & measurements This prospective cohort study included 1198 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2009. Albuminuria, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria were measured 0-6 hours after surgery. The primary outcome was AM, defined as a doubling in serum creatinine or receipt of acute dialysis during the hospital stay. Analyses were adjusted for patient characteristics, including preoperative albuminuria. Results Compared with the lowest quintile, the highest quintile of albuminuria and highest grouping of dipstick proteinuria were associated with greatest risk for AKI (adjusted relative risks [RRs], 2.97 [95% confidence interval (0), 1.20-6.91] and 2.46 [95% CI, 1.16-4.97], respectively). Higher ACR was not associated with AKI risk (highest quintile RR, 1.66 [95% Cl, 0.68-3.90]). Of the three proteinuria measures, early postoperative albuminuria improved the prediction of AKI to the greatest degree (clinical model area under the curve, 0.75; 0.81 with albuminuria). Similar improvements with albuminuria were seen for net reclassification index (0.55; P<0.001) and integrated discrimination index (0.036; P<0.001). Conclusions Higher levels of proteinuria after cardiac surgery identify patients at increased risk for AM during their hospital stay. Clin J Am Soc Nepltrol 7: 1749-1760, 2012. doi: 10.2215/CJN.13421211 C1 [Parikh, Chirag R.; Sint, Kyaw; Coca, Steven G.; Butrymowicz, Isabel] Yale Univ, Nephrol Sect, Sch Med, West Haven, CT 06516 USA. [Garg, Amit X.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Molnar, Amber O.; Garg, Amit X.] Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada. [Koyner, Jay] Univ Chicago, Pritzker Sch Med, Dept Med, Nephrol Sect, Chicago, IL 60637 USA. [Patel, Uptal D.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Patel, Uptal D.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA. [Shlipak, Michael] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Parikh, CR (reprint author), Yale Univ, Nephrol Sect, Sch Med, 950 Campbell Ave,Mail Code 151B,Bldg 35A,Room 219, West Haven, CT 06516 USA. EM chirag.parikh@yale.edu FU American Heart Association; National Heart, Lung, and Blood Institute [R01HL-085757]; CTSA grant from the National Center for Research Resources [UL1 RR024139] FX The research in this article was supported by the American Heart Association Clinical Development award and grant R01HL-085757 from the National Heart, Lung, and Blood Institute. The study was also supported by CTSA grant UL1 RR024139 from the National Center for Research Resources. NR 47 TC 13 Z9 13 U1 0 U2 5 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2012 VL 7 IS 11 BP 1749 EP 1760 DI 10.2215/CJN.13421211 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 033CO UT WOS:000310770600004 PM 22977220 ER PT J AU Vikse, BE Irgens, LM Karumanchi, SA Thadhani, R Reisaeter, AV Skjaerven, R AF Vikse, Bjorn Egil Irgens, Lorentz M. Karumanchi, S. Ananth Thadhani, Ravi Reisaeter, Anna Varberg Skjaerven, Rolv TI Familial Factors in the Association between Preeclampsia and Later ESRD SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID STAGE RENAL-DISEASE; CARDIOVASCULAR RISK-FACTORS; POPULATION-BASED COHORT; METABOLIC SYNDROME; BIRTH-WEIGHT; PREGNANCY; PREVALENCE; RECURRENCE; NORWAY; WOMEN AB Background and objectives Women with preeclampsia have increased risk of developing ESRD. This study assessed whether this can be explained by preeclampsia itself or by familial aggregation of common risk factors. Design, setting, participants, & measurements Since 1967, the Medical Birth Registry of Norway has registered data on all births in the country. By linkage with the Norwegian Population Registry, different, but overlapping, cohorts were defined: the first and second cohorts included women and a sibling (first cohort) or child (second cohort) with a registered first birth between 1967 and 2008. Similar cohorts were defined for men. The Norwegian Renal Registry provided data on ESRD from 1980 to June 2009. Results Cohort 1 was used for the main analyses and included 570,675 women, 291 of whom developed ESRD after a median 18.2 years. Compared with women without preeclampsia and no siblings with preeclampsia, women without preeclampsia but a sibling with preeclampsia had a relative risk (RR) of ESRD of 0.96 (95% confidence interval, 0.59-1.6), women with preeclampsia but no siblings with preeclampsia had a RR of 6.0 (4.4-8.1), and women with preeclampsia and a sibling with preeclampsia had a RR of 2.8 (0.88-8.6). Further analyses of women showed no increased risk of ESRD if a child had preeclampsia in first pregnancy. Conclusions Familial aggregation of risk factors does not seem to explain increased ESRD risk after preeclampsia. These findings support the hypothesis that preeclampsia per se may lead to kidney damage. Clin J Am Soc Nephrol 7: 1819-1826, 2012. doi: 10.2215/CJN.01820212 C1 [Vikse, Bjorn Egil] Haukeland Hosp, Renal Res Grp, Inst Med, Dept Med, N-5021 Bergen, Norway. [Vikse, Bjorn Egil] Univ Bergen, Renal Res Grp, Inst Med, Bergen, Norway. [Irgens, Lorentz M.; Skjaerven, Rolv] Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. [Irgens, Lorentz M.; Skjaerven, Rolv] Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. [Karumanchi, S. Ananth] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Thadhani, Ravi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Reisaeter, Anna Varberg] Oslo Univ Hosp, Norwegian Renal Registry, Nephrol Sect, Dept Transplantat Med,Rikshosp, Oslo, Norway. RP Vikse, BE (reprint author), Haukeland Hosp, Renal Res Grp, Inst Med, Dept Med, N-5021 Bergen, Norway. EM bjorn.vikse@med.uib.no FU Western Norway Regional Health authority funds FX This study has been supported by grants from the Western Norway Regional Health authority funds. NR 25 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2012 VL 7 IS 11 BP 1819 EP 1826 DI 10.2215/CJN.01820212 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 033CO UT WOS:000310770600012 PM 22956264 ER PT J AU Crowley-Matoka, M True, G AF Crowley-Matoka, Megan True, Gala TI NO ONE WANTS TO BE THE CANDY MAN: Ambivalent Medicalization and Clinician Subjectivity in Pain Management SO CULTURAL ANTHROPOLOGY LA English DT Article DE [culture of biomedicine; medicalization; subjectivity; pain] ID BODY; MEDICINE AB Pain, despite being an elemental bodily experience and the most common reason for seeking medical care, occupies a place of profound ontological and moral uncertainty in U.S. biomedicine. Taking seriously the highly charged emotionsfrustration, anger, even disgustfrequently expressed by clinicians regarding their patients with pain, this article draws on ethnographic research to explore both the origins and the implications of such anxiously ambivalent responses to pain and pain medications among the clinicians charged with treating it. Set against the recent history of pain medicine as an emergent specialty in the highly fragmented landscape of U.S. biomedicine, we examine at close ethnographic range some of the key ways that U.S. clinicians frame the experience of contending with pain in their everyday practice. Emergent from these clinician experiences are the ways in which pain and pain medications remain both incompletely medicalized and ineffectively medicalizing in U.S. biomedicine, as well as the threatening effects on what we call the pharmaceutical subjectivity of clinicians themselves of this persistently ambivalent medicalization. C1 [Crowley-Matoka, Megan] Northwestern Univ, Evanston, IL 60208 USA. [True, Gala] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [True, Gala] Univ Penn, Philadelphia, PA 19104 USA. RP Crowley-Matoka, M (reprint author), Northwestern Univ, Evanston, IL 60208 USA. NR 46 TC 12 Z9 12 U1 1 U2 11 PU SOC CULTURAL ANTHROPOLOGY PI HOUSTON PA DEPT ANTHROPOLOGY, MS-20, RICE UNIV, PO BOX 1892, HOUSTON, TX 77251 USA SN 0886-7356 EI 1548-1360 J9 CULT ANTHROPOL JI Cult. Anthropol. PD NOV PY 2012 VL 27 IS 4 BP 689 EP 712 DI 10.1111/j.1548-1360.2012.01167.x PG 24 WC Anthropology SC Anthropology GA 037HK UT WOS:000311092600007 ER PT J AU Glazer, NL Macy, EM Lumley, T Smith, NL Reiner, AP Psaty, BM King, GL Tracy, RP Siscovick, DS AF Glazer, Nicole L. Macy, Elizabeth M. Lumley, Thomas Smith, Nicholas L. Reiner, Alex P. Psaty, Bruce M. King, George L. Tracy, Russell P. Siscovick, David S. TI Transforming growth factor beta-1 and incidence of heart failure in older adults: The Cardiovascular Health Study SO CYTOKINE LA English DT Article DE Transforming growth factor-beta; Heart failure; Fibrosis; Growth factors; Cardiac remodeling ID WEIGHTED LIKELIHOOD; DISEASE; CARDIOMYOPATHY; MECHANISMS; FIBROSIS AB Context: Transforming growth factor-betal (TGF-B1) is a highly pleiotropic cytokine whose functions include a central role in the induction of fibrosis. Objective: To investigate the hypothesis that elevated plasma levels of TGF-B1 are positively associated with incident heart failure (HF). Participants and methods: The hypotheses were tested using a two-phase case-control study design, ancillary to the Cardiovascular Health Study - a longitudinal, population-based cohort study. Cases were defined as having an incident HF event after their 1992-1993 exam and controls were free of HF at follow-up. TGF-B1 was measured using plasma collected in 1992-1993 and data from 89 cases and 128 controls were used for analysis. The association between TGF-B1 and risk of HF was evaluated using the weighted likelihood method, and odds ratios (OR) for risk of HF were calculated for TGF-B1 as a continuous linear variable and across quartiles of TGF-B1. Results: The OR for HF was 1.88 (95% confidence intervals [CI] 1.26-2.81) for each nanogram increase in TGF-B1, and the OR for the highest quartile (compared to the lowest) of TGF-B1 was 5.79 (95% CI 1.65-20.34), after adjustment for age, sex. C-reactive protein, platelet count and digoxin use. Further adjustment with other covariates did not change the results. Conclusions: Higher levels of plasma TGF-B1 were associated with an increased risk of incident heart failure among older adults. However, further study is needed in larger samples to confirm these findings. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Glazer, Nicole L.; Smith, Nicholas L.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Macy, Elizabeth M.; Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Macy, Elizabeth M.; Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. [Lumley, Thomas] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Smith, Nicholas L.; Reiner, Alex P.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smith, Nicholas L.] Vet Adm Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. [Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Glazer, NL (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM nlglazer@bu.edu FU National Heart, Lung, and Blood Institute [T32 HL00790, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL080295R01]; Leducq Foundation, Paris, France; National Institute of Neurological Disorders and Stroke FX The research reported in this article was supported by Cardiovascular Disease Epidemiology Training Grant T32 HL00790, contract numbers N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, Grant Nos. U01 HL080295 and R01 HL080295R01 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. A full list of principal CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. This research was also supported by a private grant from the Leducq Foundation, Paris, France for the development of Transatlantic Networks of Excellence in Cardiovascular Research. NR 15 TC 6 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD NOV PY 2012 VL 60 IS 2 BP 341 EP 345 DI 10.1016/j.cyto.2012.07.013 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 029KL UT WOS:000310494300005 PM 22878343 ER PT J AU Smith, KW Braun, JM Williams, PL Ehrlich, S Correia, KF Calafat, AM Ye, XY Ford, J Keller, M Meeker, JD Hauser, R AF Smith, Kristen W. Braun, Joe M. Williams, Paige L. Ehrlich, Shelley Correia, Katharine F. Calafat, Antonia M. Ye, Xiaoyun Ford, Jennifer Keller, Myra Meeker, John D. Hauser, Russ TI Predictors and Variability of Urinary Paraben Concentrations in Men and Women, Including before and during Pregnancy SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarker; exposure science; female; male; parabens; partners; predictors; pregnancy; variability ID MALE REPRODUCTIVE-SYSTEM; BISPHENOL-A CONCENTRATIONS; PHTHALATE METABOLITE; TEMPORAL VARIABILITY; BUTYL PARABEN; HUMAN HEALTH; HUMANS; PRESERVATIVES; BUTYLPARABEN; EXPOSURE AB BACKGROUND: Parabens are suspected endocrine disruptors and ubiquitous preservatives used in personal care products, pharmaceuticals, and foods. No studies have assessed the variability of parabens in women, including during pregnancy. OBJECTIVE: We evaluated predictors and variability of urinary paraben concentrations. METHODS: We measured urinary concentrations of methyl (MP), propyl (PP), and butyl paraben (BP) among couples from a fertility center. Mixed-effects regression models were fit to examine demographic predictors of paraben concentrations and to calculate intraclass correlation coefficients (ICCs). RESULTS: Between 2005 and 2010, we collected 2,721 spot urine samples from 245 men and 408 women. The median concentrations were 112 mu g/L (MP), 24.2 mu g/L (PP), and 0.70 mu g/L (BP). Urinary MP and PP concentrations were 4.6 and 7.8 times higher in women than men, respectively, and concentrations of both MP and PP were 3.8 times higher in African Americans than Caucasians. MP and PP concentrations we CI re slightly more variable in women (ICC = 0.42, 0.43) than men (ICC = 0.54, 0.51), and were weakly correlated between partners (r = 0.27-0.32). Among 129 pregnant women, urinary paraben concentrations were 25-45% lower during pregnancy than before pregnancy, and MP and PP concentrations were more variable (ICCs of 0.38 and 0.36 compared with 0.46 and 0.44, respectively). CONCLUSIONS: Urinary paraben concentrations were more variable in women compared with men, and during pregnancy compared with before pregnancy. However, results for this study population suggest that a single urine sample may reasonably represent an individual's exposure over several months, and that a single sample collected during pregnancy may reasonably classify gestational exposure. C1 [Smith, Kristen W.; Braun, Joe M.; Ehrlich, Shelley; Ford, Jennifer; Keller, Myra; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Correia, Katharine F.] Brigham & Womens Hosp, Div Reprod Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Meeker, John D.] Univ Michigan, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Hauser, Russ] Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Hauser, R (reprint author), 665 Huntington Ave,Bldg 1,14th Floor, Boston, MA 02115 USA. EM rhauser@hsph.harvard.edu RI Braun, Joseph/H-8649-2014; Ehrlich , Shelley/L-6991-2015; OI Meeker, John/0000-0001-8357-5085 FU National Institute of Environmental Health Sciences, National Institutes of Health [ES009718, ES000002, T32ES007069] FX The work was supported by grants ES009718, ES000002, and T32ES007069 from the National Institute of Environmental Health Sciences, National Institutes of Health. NR 29 TC 53 Z9 53 U1 4 U2 59 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2012 VL 120 IS 11 BP 1538 EP 1543 DI 10.1289/ehp.1104614 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 036ZE UT WOS:000311070000022 PM 22721761 ER PT J AU Salinsky, M Evrard, C Storzbach, D Pugh, MJ AF Salinsky, Martin Evrard, Collette Storzbach, Daniel Pugh, Mary Jo TI Psychiatric comorbidity in veterans with psychogenic seizures SO EPILEPSY & BEHAVIOR LA English DT Article DE Epilepsy; Psychogenic seizures; Veterans; Post-traumatic stress disorder ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN-INJURY; NONEPILEPTIC SEIZURES; VIDEO-EEG; EPILEPSY; HEALTH; PREVALENCE; DIAGNOSIS; SYMPTOMS; HISTORY AB Psychogenic non-epileptic seizures (PNES) are frequently encountered in epilepsy monitoring units (EMU) at Veterans Affairs Medical Centers (VAMCs) and cause significant long-term disability. An understanding of psychiatric factors associated with PNES could aid in earlier diagnosis and treatment. We studied 50 consecutive veterans diagnosed with PNES and 37 veterans diagnosed with epileptic seizures (ES), evaluated at a VAMC EMU. We reviewed all available mental health evaluations prior to EMU evaluation. Univariate comparisons included axis I diagnoses, axis II diagnoses, and psychiatric hospitalizations. Predictive models of seizure classification were evaluated by logistic regression. A diagnosis of post-traumatic stress disorder (PTSD) preceded the diagnosis of PNES in 58% of patients and the diagnosis of ES in 13.5% (p<0.001). On logistic regression, PTSD was the only significant psychiatric diagnosis (odds ratio 9.2). Major depression and alcohol abuse were common diagnoses but did not differentiate PNES and ES groups. Published by Elsevier Inc. C1 [Salinsky, Martin; Evrard, Collette; Storzbach, Daniel] Portland VA Med Ctr, Portland, OR USA. [Salinsky, Martin] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Pugh, Mary Jo] San Antonio Vet Affairs Med Ctr, San Antonio, TX USA. RP Salinsky, M (reprint author), 3181 SW Sam Jackson Pk Rd,CR 120, Portland, OR 97239 USA. EM Salinsky@ohsu.edu OI Pugh, Mary Jo/0000-0003-4196-7763 FU Portland VA Medical Center FX This material is the result of work supported with resources and the use of facilities at the Portland VA Medical Center. NR 30 TC 18 Z9 19 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2012 VL 25 IS 3 BP 345 EP 349 DI 10.1016/j.yebeh.2012.07.013 PG 5 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 035BM UT WOS:000310917000009 PM 23103308 ER PT J AU Faria, P Fregni, F Sebastiao, F Dias, AI Leal, A AF Faria, Paula Fregni, Felipe Sebastiao, Fernando Dias, Ana I. Leal, Alberto TI Feasibility of focal transcranial DC polarization with simultaneous EEG recording: Preliminary assessment in healthy subjects and human epilepsy SO EPILEPSY & BEHAVIOR LA English DT Article DE EEG; tDCS; Polarization; Epilepsy; Transcranial; Safety ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; POLARIZING CURRENTS; BRAIN POLARIZATION; CEREBRAL CORTEX; CLINICAL-TRIAL; EXCITABILITY; TDCS; RAT AB We aimed to investigate the feasibility of an experimental system for simultaneous transcranial DC stimulation (tDCS) and EEG recording in human epilepsy. We report tolerability of this system in a cross-over controlled trial with 15 healthy subjects and preliminary effects of its use, testing repeated tDCS sessions, in two patients with drug-refractory Continuous Spike-Wave Discharges During Slow Sleep (CSWS). Our system combining continuous recording of the EEG with tDCS allows detailed evaluation of the interictal activity during the entire process. Stimulation with 1 mA was well-tolerated in both healthy volunteers and patients with refractory epilepsy. The large reduction in interictal epileptiform EEG discharges in the two subjects with epilepsy supports further investigation of tDCS using this combined method of stimulation and monitoring in epilepsy. Continuous monitoring of epileptic activity throughout tDCS improves safety and allows detailed evaluation of epileptic activity changes induced by tDCS in patients. (C) 2012 Elsevier Inc. All rights reserved. C1 [Faria, Paula] Polytech Inst Leiria, Ctr Rapid & Sustainable Prod Dev, Leiria, Portugal. [Faria, Paula; Sebastiao, Fernando] Polytech Inst Leiria, Sch Technol & Management, Leiria, Portugal. [Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Sebastiao, Fernando] Univ Tras Os Montes & Alto Douro, Ctr Math, CM UTAD, Vila Real, Portugal. [Dias, Ana I.] Hosp Dona Estefania, Dept Pediat Neurol, Lisbon, Portugal. [Leal, Alberto] Ctr Hosp Psiquiatr Lisboa, Dept Neurophysiol, Lisbon, Portugal. RP Faria, P (reprint author), Campus 2,Apartado 4163, P-2411901 Alto Do Vieiro, Leiria, Portugal. EM paula.faria@ipleiria.pt RI Faria, Paula/N-2655-2013; OI Faria, Paula/0000-0003-1474-9496; Sebastiao, Fernando/0000-0002-8792-4649; Leal, Alberto/0000-0002-3178-2530 FU FCT [SFRH/BD/29020/2006]; CIMIT (Center for Integration of Medicine and Innovative Technology); Tecnifar SA FX We are grateful to Daniela Dias, Heloisa Silva, and Ricardo Lopes for the technical support on the experimental acquisition of data and to Pedro Cavaleiro Miranda for the loan of the stimulation device used in the tDCS application. Paula Faria gratefully acknowledges the support by FCT, under grant No. SFRH/BD/29020/2006. Felipe Fregni is supported by a grant from CIMIT (Center for Integration of Medicine and Innovative Technology). Alberto Leal is supported by a grant for research in epilepsy from Tecnifar SA. NR 31 TC 27 Z9 28 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 EI 1525-5069 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2012 VL 25 IS 3 BP 417 EP 425 DI 10.1016/j.yebeh.2012.06.027 PG 9 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 035BM UT WOS:000310917000022 PM 23123281 ER PT J AU Fujikawa, DG Licht, EA Jacobsen, RH AF Fujikawa, Denson G. Licht, Eliot A. Jacobsen, Rebecca H. TI Chronic epileptic encephalopathy in adult patients with bilaterally synchronous frequent and/or prolonged subclinical epileptiform discharges SO EPILEPSY & BEHAVIOR LA English DT Article DE Epileptic encephalopathy; Idiopathic generalized epilepsy; Spike and slow-wave discharges; Subclinical epileptiform discharges; Adults ID IDIOPATHIC GENERALIZED EPILEPSY; JUVENILE MYOCLONIC EPILEPSY; COGNITIVE DYSFUNCTION; ONSET; CHILDREN AB We followed four patients with infrequent convulsive seizures for four to 10 years, with periodic EEGs and neuropsychological tests. All four had bursts of frontally predominant, bilaterally synchronous 1.5-3-Hz spike or polyspike and slow-wave discharges (SWDs) that initially comprised 15% to 88% but were reduced to 5% or less of total EEG time with appropriate antiepileptic drugs. Case 1 showed a 30-point improvement in his verbal WAIS-R score and Case 4 a 21-point improvement in his performance WAIS-R score, over nine-and five-year periods, respectively, with normalization of frontal executive function. Cases 2 and 3 showed no improvement in frontal executive dysfunction despite being free of SWDs for nine and five years, respectively. These patients had variable degrees of epileptic encephalopathy and subclinical SWDs. They illustrate the importance of minimizing the occurrence of SWDs with appropriate antiepileptic drugs and long-term monitoring with neuropsychological tests because chronic cognitive deficits are potentially reversible. Published by Elsevier Inc. C1 [Fujikawa, Denson G.; Licht, Eliot A.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, North Hills, CA USA. [Jacobsen, Rebecca H.] VA Greater Los Angeles Healthcare Syst, Dept Mental Hlth, North Hills, CA USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Fujikawa, Denson G.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Fujikawa, DG (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Neurol, North Hills, CA USA. EM dfujikaw@ucla.edu NR 17 TC 2 Z9 2 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2012 VL 25 IS 3 BP 442 EP 448 DI 10.1016/j.yebeh.2012.08.001 PG 7 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 035BM UT WOS:000310917000026 PM 23021092 ER PT J AU Shafer, PO Buelow, JM Noe, K Shinnar, R Dewar, S Levisohn, PM Dean, P Ficker, D Pugh, MJ Barkley, GL AF Shafer, Patricia O. Buelow, Janice M. Noe, Katherine Shinnar, Ruth Dewar, Sandra Levisohn, Paul M. Dean, Patricia Ficker, David Pugh, Mary Jo Barkley, Gregory L. TI A consensus-based approach to patient safety in epilepsy monitoring units: Recommendations for preferred practices SO EPILEPSY & BEHAVIOR LA English DT Article DE Patient safety; Epilepsy monitoring units; Delphi methodology; Epilepsy; Video-EEG telemetry; Expert consensus; Seizure precautions; Seizure observation ID TEMPORAL-LOBE EPILEPSY; LONG-TERM; STATUS EPILEPTICUS; POSTICTAL PSYCHOSIS; SEIZURE OCCURRENCE; FREQUENCY; GUIDELINES; MANAGEMENT; INDUCTION; SYMPTOMS AB Patients in an epilepsy monitoring unit (EMU) with video-EEG telemetry have a risk for seizure emergencies, injuries and adverse events, which emphasizes the need for strategies to prevent avoidable harm. An expert consensus process was used to establish recommendations for patient safety in EMUs. Workgroups analyzed literature and expert opinion regarding seizure observation, seizure provocation, acute seizures, and activity/environment. A Delphi methodology was used to establish consensus for items submitted by these workgroups. Fifty-three items reached consensus and were organized into 30 recommendations. High levels of agreement were noted for items pertaining to orientation, training, communication, seizure precautions, individualized plans, and patient/family education. It was agreed that seizure observation should include direct observation or use of closed-circuit camera. The use of continuous observation was strongest in patients with invasive electrodes, at high risk for injury, or undergoing AED withdrawal. This process provides a first step in establishing EMU safety practices. (C) 2012 Elsevier Inc. All rights reserved. C1 [Shafer, Patricia O.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Buelow, Janice M.] Indiana Univ, Sch Nursing, Indianapolis, IN 46202 USA. [Noe, Katherine] Mayo Clin, Dept Epilepsy & Neurol, Phoenix, AZ 85054 USA. [Shinnar, Ruth] Montefiore Med Ctr, Bronx, NY 10467 USA. [Dewar, Sandra] Univ Calif Los Angeles, Seizure Disorder Ctr, Los Angeles, CA 90025 USA. [Levisohn, Paul M.] Childrens Hosp Colorado, Aurora, CO 80045 USA. [Dean, Patricia] Miami Childrens Hosp, Inst Brain, Epilepsy Program, Miami, FL 33155 USA. [Ficker, David] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH 45267 USA. [Pugh, Mary Jo] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Pugh, Mary Jo] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Barkley, Gregory L.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. RP Shafer, PO (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. EM poshafer@bidmc.harvard.edu; jbuelow@iupui.edu; noe.katherine@mayo.edu; codell@sprynet.com; sdewar@mednet.ucla.edu; paul.levisohn@childrenscolorado.org; pat.dean@mch.com; fickerdm@ucmail.uc.edu; pughm@uthscsa.edu; barkley@neuro.hfh.edu OI Pugh, Mary Jo/0000-0003-4196-7763 NR 55 TC 20 Z9 20 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2012 VL 25 IS 3 BP 449 EP 456 DI 10.1016/j.yebeh.2012.07.014 PG 8 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 035BM UT WOS:000310917000027 PM 22999858 ER PT J AU Le Cesne, A Cresta, S Maki, RG Blay, JY Verweij, J Poveda, A Casali, PG Balana, C Schoffski, P Grosso, F Lardelli, P Nieto, A Alfaro, V Demetri, GD AF Le Cesne, Axel Cresta, Sara Maki, Robert G. Blay, Jean Yves Verweij, Jaap Poveda, Andres Casali, Paolo G. Balana, Carme Schoffski, Patrick Grosso, Federica Lardelli, Pilar Nieto, Antonio Alfaro, Vicente Demetri, George D. TI A retrospective analysis of antitumour activity with trabectedin in translocation-related sarcomas SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Antitumour activity; Chimeric fusion oncoproteins; Chromosomal translocation; Sarcoma; Trabectedin ID SOFT-TISSUE SARCOMA; RECURRENT OVARIAN-CANCER; PHASE-II; EUROPEAN ORGANIZATION; MYXOID LIPOSARCOMAS; ECTEINASCIDIN 743; ET-743; BONE; CHEMOTHERAPY; PLATINUM AB Aims: Approximately 20% of soft tissue sarcomas (STS) have subtype-specific chromosomal translocations; these generate chimeric oncoproteins which can act as abnormal transcription factors. Since trabectedin can bind to DNA and displace transcription factors, antitumour activity was explored in translocation-related sarcoma (TRS) subtypes. Methods: The current retrospective pooled analysis includes data from 81 patients with TRS treated in 8 phase II trials. Results: TRS subtypes were: synovial sarcoma (SS, n = 45), myxoid-round cell liposarcoma (MRC-L-sarcoma, n = 27), alveolar soft part sarcoma (ASPS, n = 4), endometrial stromal sarcoma (ESS, n = 3) and clear cell sarcoma (CCS, n = 2). All but one patient had received prior chemotherapy (median of 2 lines). Patients received a median of 4 trabectedin cycles (range, 1-48; median dose intensity = 0.40 mg/m(2)/week). Partial responses according to Response Evaluation Criteria in Solid Tumours (RECIST) occurred in 8 patients (ORR = 10%; 95% CI, 4-19%): four in MRC-L-sarcoma; three in SS and one in ESS. Tumour control rate (ORR plus stable disease) was 59% (95% CI, 48-70%). Median PFS was 4.1 months (6-month PFS rate = 40%). Median overall survival was 17.4 months (survival rate at 12 months = 60%). Trabectedin had a manageable safety profile. Conclusion: Trabectedin demonstrates encouraging disease control in TRS. Since these promising results were generally noted in patients following chemotherapy, a phase III randomised trial in first-line is ongoing to compare trabectedin with doxorubicin-based chemotherapy in patients with TRS. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Le Cesne, Axel] Inst Gustave Roussy, Dept Med Oncol, F-94805 Villejuif, France. [Cresta, Sara] Fdn Ist Nazl Tumori, Dept Oncol, Milan, Italy. [Maki, Robert G.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Blay, Jean Yves] Ctr Leon Berard, Dept Med Oncol, F-69373 Lyon, France. [Verweij, Jaap] Erasmus Univ, Med Ctr, Daniel den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. [Poveda, Andres] Inst Valenciano Oncol, Dept Med Oncol, Valencia, Spain. [Casali, Paolo G.] Inst Nazl Tumori Oncol, Dept Canc Med, Milan, Italy. [Balana, Carme] Inst Catala Oncol Germans Trias & Pujol, Med Oncol Serv, Badalona, Spain. [Schoffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Gen Med Oncol, Louvain, Belgium. [Schoffski, Patrick] Katholieke Univ Leuven, Univ Hosp Leuven, Expt Oncol Lab, Louvain, Belgium. [Grosso, Federica] SS Antonio & Biagio & C Arrigo Gen Hosp, Dept Oncol, Alessandria, Italy. [Lardelli, Pilar; Nieto, Antonio; Alfaro, Vicente] PharmaMar, Clin R&D, Colmenar Viejo Madrid, Spain. [Demetri, George D.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA USA. RP Le Cesne, A (reprint author), Inst Gustave Roussy, Dept Med Oncol, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. EM lecesne@igr.fr RI BALANA, CARMEN/A-6828-2012; Blay, Jean-Yves/N-3966-2016; Cresta, Sara/B-8588-2017; casali, Paolo Giovanni/D-1524-2017 OI BALANA, CARMEN/0000-0003-0771-0390; Blay, Jean-Yves/0000-0001-7190-120X; Cresta, Sara/0000-0002-6830-0662; casali, Paolo Giovanni/0000-0003-4056-8023 FU PharmaMar; PharmaMar, Madrid, Spain FX A. Le Cesne received honoraria from PharmaMar. R. G. Maki received research support and consulting fees (participation in data safety monitoring board) from PharmaMar. J.Y. Blay received research support and honoraria from PharmaMar. P. Lardelli, V. Alfaro and A. Nieto are employees of PharmaMar. P Lardelli and A. Nieto own stock of PharmaMar. G. D. Demetri received research support to Dana-Farber Cancer Institute for specific clinical trial agreements in the sarcoma unit, honoraria as consultant and uncompensated regulatory presentation support from Johnson & Johnson.; Financial support for this analysis was provided by PharmaMar, Madrid, Spain. NR 54 TC 46 Z9 47 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2012 VL 48 IS 16 BP 3036 EP 3044 DI 10.1016/j.ejca.2012.05.012 PG 9 WC Oncology SC Oncology GA 030KH UT WOS:000310569100012 PM 22749255 ER PT J AU Han, R Beppu, H Lee, YK Georgopoulos, K Larue, L Li, E Weiner, L Brissette, JL AF Han, Rong Beppu, Hideyuki Lee, Yun-Kyoung Georgopoulos, Katia Larue, Lionel Li, En Weiner, Lorin Brissette, Janice L. TI A pair of transmembrane receptors essential for the retention and pigmentation of hair SO GENESIS LA English DT Article DE anagen; catagen; telogen; terminal differentiation; melanosome; Bmp signaling ID BONE MORPHOGENETIC PROTEIN-4; II RECEPTOR; SIGNALING PATHWAYS; TRANSGENIC MICE; SHAFT DIFFERENTIATION; OSTEOGENIC PROTEIN-1; GROWTH-INHIBITION; ACTIVIN RECEPTORS; KINASE RECEPTORS; SKIN DEVELOPMENT AB Hair follicles are simple, accessible models for many developmental processes. Here, using mutant mice, we show that Bmpr2, a known receptor for bone morphogenetic proteins (Bmps), and Acvr2a, a known receptor for Bmps and activins, are individually redundant but together essential for multiple follicular traits. When Bmpr2/Acvr2a function is reduced in cutaneous epithelium, hair follicles undergo rapid cycles of hair generation and loss. Alopecia results from a failure to terminate hair development properly, as hair clubs never form, and follicular retraction is slowed. Hair regeneration is rapid due to premature activation of new hair-production programs. Hair shafts differentiate aberrantly due to impaired arrest of medullary-cell proliferation. When Bmpr2/Acvr2a function is reduced in melanocytes, gray hair develops, as melanosomes differentiate but fail to grow, resulting in organelle miniaturization. We conclude that Bmpr2 and Acvr2a normally play cell-type-specific, necessary roles in organelle biogenesis and the shutdown of developmental programs and cell division. genesis 118, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Han, Rong; Lee, Yun-Kyoung; Weiner, Lorin; Brissette, Janice L.] Suny Downstate Med Ctr, Dept Cell Biol, Brooklyn, NY 11203 USA. [Han, Rong; Georgopoulos, Katia; Weiner, Lorin; Brissette, Janice L.] Harvard Univ, Sch Med, Charlestown, MA USA. [Han, Rong; Georgopoulos, Katia; Weiner, Lorin; Brissette, Janice L.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Beppu, Hideyuki] Toyama Univ, Dept Clin & Mol Pathol, Toyama 930, Japan. [Larue, Lionel] Inst Curie, INSERM, U1021, CNRS,Dev Genet Melanocytes UMR3347, F-91405 Orsay, France. [Li, En] Novartis Inst Biomed Res, Cambridge, MA USA. RP Brissette, JL (reprint author), Suny Downstate Med Ctr, Dept Cell Biol, 450 Clarkson Ave,Box 44, Brooklyn, NY 11203 USA. EM lorin.weiner@downstate.edu; janice.brissette@downstate.edu RI Larue, Lionel/F-7355-2013; Larue, Lionel/I-6532-2016; OI Han, Rong/0000-0002-5766-8277 FU NIH/NIAMS [AR045284, AR055218]; NIH/NICHD [HD035286]; Cutaneous Biology Research Center via the Massachusetts General Hospital/Shiseido Co. Ltd.; Ligue Nationale Contre le Cancer (Equipe labellisee) FX Contract grant sponsor: NIH/NIAMS; contract grant numbers: AR045284 (JLB), AR055218 (JLB); Contract grant sponsor: NIH/NICHD; contract grant number: HD035286 (EL, JLB).; We thank George E. Rogers for antibodies to trichohyalin, Yimin Ruan for technical assistance, Pierre Chambon for K14-Cre mice, and Mary McKee and Wei Quan for assistance with electron microscopy. This work was supported by grants to J.L.B. from the Cutaneous Biology Research Center via the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement. L. L. was supported by the Ligue Nationale Contre le Cancer (Equipe labellisee). NR 69 TC 3 Z9 3 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-954X J9 GENESIS JI Genesis PD NOV PY 2012 VL 50 IS 11 BP 783 EP 800 DI 10.1002/dvg.22039 PG 18 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 041ML UT WOS:000311405800001 PM 22611050 ER PT J AU Weisberg, E Sattler, M AF Weisberg, Ellen Sattler, Martin TI A novel combination therapy approach for the treatment of acute myeloid leukemia: the multi-kinase inhibitor sorafenib and the HDM2 inhibitor nutlin-3 SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material ID RENAL-CELL CARCINOMA; P53 MUTATIONS; MUTANT FLT3; PKC412; TARGET; GENE C1 [Weisberg, Ellen; Sattler, Martin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weisberg, E (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ellenweis@yahoo.com NR 13 TC 2 Z9 2 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2012 VL 97 IS 11 BP 1620 EP 1621 DI 10.3324/haematol.2012.078451 PG 2 WC Hematology SC Hematology GA 043WL UT WOS:000311581300006 PM 23125243 ER PT J AU Touil, S Rosenzwajg, M Landau, DA Le Corvoisier, P Charlotte, F Klatzmann, D Maury, S Cohen, JL AF Touil, Soumia Rosenzwajg, Michelle Landau, Dan Avi Le Corvoisier, Philippe Charlotte, Frederic Klatzmann, David Maury, Sebastien Cohen, Jose L. TI Depletion of T regulatory cells through selection of CD127-positive cells results in a population enriched in memory T cells: implications for anti-tumor cell therapy SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE CD127 positive selection; Treg; alloreactivity; donor lymphocyte infusion ID VERSUS-HOST-DISEASE; BONE-MARROW TRANSPLANTATION; LEUKEMIA REACTIONS; EXPRESSION; GVHD; INFUSION; FOXP3; MICE AB Background Donor lymphocyte infusions can induce remissions in patients with relapse after allogeneic hematopoietic stem cell transplantation. Nevertheless, some grafted patients never display any signs of alloreactivity, either following allogeneic hematopoietic stem cell transplantation or after donor lymphocyte infusions. Consequently, they do not develop graft-versus-host disease and frequently do not respond to donor lymphocyte infusions. In a recently published clinical trial, we observed that elimination of CD4(+)CD25(+)Foxp3(+) natural regulatory T cells from the donor lymphocyte product could improve alloreactivity and the associated anti-tumor effect in a small proportion of patients with relapsed hematologic malignancies. Here, we aimed to improve the effect of donor lymphocyte infusion by modifying the procedure for depletion of T regulatory cells. Design and Methods We directly compared depletion of regulatory T cells from human peripheral blood mononuclear cells achieved by selection of CD127-positive cells or by selection of CD25-negative cells. We tested the manipulated products (i) in vitro in mixed lymphocyte reactions and against pathogen-derived recall antigens and (ii) in vivo in experimental graft-versus-host disease. Results In vitro, we found that depletion of regulatory T cells through CD127 positive selection improved both alloreactive and pathogen-specific immune responses. In vivo, we observed accelerated donor T-cell division and enhanced graft-versus-host disease due to efficient regulatory T-cell depletion accompanied by enrichment in memory T cells. Conclusions Our results show that the strategy of CD127 positive selection is an efficient way of eliminating regulatory T cells from donor lymphocyte infusions and improves alloreactivity. This supports the investigation of CD127 positive selection in place of elimination of CD25-positive cells for clinical applications. C1 [Maury, Sebastien; Cohen, Jose L.] Hop Henri Mondor, INSERM, U955, IMRB, F-94010 Creteil, France. [Touil, Soumia; Charlotte, Frederic; Klatzmann, David] Univ Paris 06, Paris, France. [Touil, Soumia; Charlotte, Frederic; Klatzmann, David] CNRS, I3 UMR7211, Paris, France. [Rosenzwajg, Michelle; Klatzmann, David] INSERM, U959 I3, Paris, France. [Rosenzwajg, Michelle; Klatzmann, David] Hop La Pitie Salpetriere, AP HP, Serv Biotherapie, Paris, France. [Landau, Dan Avi] Yale Univ, Dept Hematol, Yale Canc Ctr, New Haven, CT USA. [Landau, Dan Avi] Dana Farber Inst, Dept Med Oncol, Boston, MA USA. [Landau, Dan Avi] Broad Inst MIT & Harvard, Cambridge, MA USA. [Le Corvoisier, Philippe; Maury, Sebastien; Cohen, Jose L.] Univ Paris Est Creteil, Fac Med Creteil, Paris, France. [Le Corvoisier, Philippe; Maury, Sebastien; Cohen, Jose L.] Grp Hosp Henri Mondor, AP HP, Creteil, France. [Maury, Sebastien; Cohen, Jose L.] INSERM, CIC BT, Creteil, France. RP Maury, S (reprint author), Hop Henri Mondor, INSERM, U955, IMRB, 51 Ave Mal Lattre de Tassigny, F-94010 Creteil, France. EM sebastien.maury@hmn.aphp.fr FU APP recherche clinique translationnelle Inserm-DHOS-INCA; Agence de la Biomedecine; French government FX this work was supported by "APP recherche clinique translationnelle Inserm-DHOS-INCA 2008" and "Agence de la Biomedecine". ST is supported by a grant from the French government. NR 26 TC 6 Z9 6 U1 0 U2 6 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2012 VL 97 IS 11 BP 1678 EP 1685 DI 10.3324/haematol.2011.056374 PG 8 WC Hematology SC Hematology GA 043WL UT WOS:000311581300014 PM 22581007 ER PT J AU Saeidi, N Nestoridi, E Kucharczyk, J Uygun, MK Yarmush, ML Stylopoulos, N AF Saeidi, N. Nestoridi, E. Kucharczyk, J. Uygun, M. K. Yarmush, M. L. Stylopoulos, N. TI Sleeve gastrectomy and Roux-en-Y gastric bypass exhibit differential effects on food preferences, nutrient absorption and energy expenditure in obese rats SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE gastric bypass; metabolism; metabolic surgery; energy expenditure; animal models; sleeve gastrectomy ID VERTICAL BANDED GASTROPLASTY; CONDITIONED TASTE-AVERSION; BARIATRIC SURGERY; WEIGHT-LOSS; CALORIC RESTRICTION; BODY-COMPOSITION; DIETARY-INTAKE; BILIOPANCREATIC DIVERSION; PHYSICAL-ACTIVITY; METAANALYSIS AB OBJECTIVE: All available treatments directed towards obesity and obesity-related complications are associated with suboptimal effectiveness/invasiveness ratios. Pharmacological, behavioral and lifestyle modification treatments are the least invasive, but also the least effective options, leading to modest weight loss that is difficult to maintain long-term. Gastrointestinal weight loss surgery (GIWLS) is the most effective, leading to >60-70% of excess body weight loss, but also the most invasive treatment available. Sleeve gastrectomy (SGx) and Roux-en-Y gastric bypass (RYGB) are the two most commonly performed GIWLS procedures. The fundamental anatomic difference between SGx and RYGB is that in the former procedure, only the anatomy of the stomach is altered, without surgical reconfiguration of the intestine. Therefore, comparing these two operations provides a unique opportunity to study the ways that different parts of the gastrointestinal (GI) tract contribute to the regulation of physiological processes, such as the regulation of body weight, food intake and metabolism. DESIGN: To explore the physiologic mechanisms of the two procedures, we used rodent models of SGx and RYGB to study the effects of these procedures on body weight, food intake and metabolic function. RESULTS: Both SGx and RYGB induced a significant weight loss that was sustained over the entire study period. SGx-induced weight loss was slightly lower compared with that observed after RYGB. SGx-induced weight loss primarily resulted from a substantial decrease in food intake and a small increase in locomotor activity. In contrast, rats that underwent RYGB exhibited a substantial increase in non-activity-related (resting) energy expenditure and a modest decrease in nutrient absorption. Additionally, while SGx-treated animals retained their preoperative food preferences, RYGB-treated rats experienced a significant alteration in their food preferences. CONCLUSIONS: These results indicate a fundamental difference in the mechanisms of weight loss between SGx and RYGB, suggesting that the manipulation of different parts of the GI tract may lead to different physiologic effects. Understanding the differences in the physiologic mechanisms of action of these effective treatment options could help us develop less invasive new treatments against obesity and obesity-related complications. International Journal of Obesity (2012) 36, 1396-1402; doi:10.1038/ijo.2012.167; published online 9 October 2012 C1 [Stylopoulos, N.] Harvard Univ, Childrens Hosp Boston, Ctr Basic & Translat Obes Res, Div Endocrinol,Ctr Life Sci,Med Sch, Boston, MA 02115 USA. [Saeidi, N.; Uygun, M. K.; Yarmush, M. L.] Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Sch Med, Boston, MA 02115 USA. [Saeidi, N.; Uygun, M. K.; Yarmush, M. L.] Harvard Univ, Shriners Hosp Children, Sch Med, Boston, MA 02115 USA. RP Stylopoulos, N (reprint author), Harvard Univ, Childrens Hosp Boston, Ctr Basic & Translat Obes Res, Div Endocrinol,Ctr Life Sci,Med Sch, 3 Blackfan Circle, Boston, MA 02115 USA. EM Nicholas.Stylopoulos@childrens.harvard.edu FU NIDDK NIH HHS [F32 DK095558] NR 45 TC 31 Z9 31 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 2012 VL 36 IS 11 BP 1396 EP 1402 DI 10.1038/ijo.2012.167 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 037KR UT WOS:000311103500004 PM 23044855 ER PT J AU Kellogg, DL Zhao, JL Wu, YB Johnson, JM AF Kellogg, Dean L., Jr. Zhao, Joan L. Wu, Yubo Johnson, John M. TI Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE laser-Doppler flowmetry; VPAC2; PAC1; thermoregulation; microdialysis ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; SYNTHASE CONTROL MECHANISMS; SKIN BLOOD-FLOW; VASCULAR-RESPONSES; IN-VIVO; PHARMACOLOGY; EXERCISE; INHIBITION; ROLES AB Kellogg DL Jr, Zhao JL, Wu Y, Johnson JM. Nitric oxide and receptors for VIP and PACAP in cutaneous active vasodilation during heat stress in humans. J Appl Physiol 113: 1512-1518, 2012. First published September 6, 2012; doi:10.1152/japplphysiol.00859.2012.-VPAC2 receptors sensitive to vasoactive intestinal polypeptide (VIP) and pituitary adenylyl cyclase activating polypeptide (PACAP), PAC1 receptors sensitive to PACAP, and nitric oxide (NO) generation by NO synthase (NOS) are all implicated in cutaneous active vasodilation (AVD) through incompletely defined mechanisms. We hypothesized that VPAC2/PAC1 receptor activation and NO are synergistic and interdependent in AVD and tested our hypothesis by examining the effects of VPAC2/PAC1 receptor blockade with and without NOS inhibition during heat stress. The VPAC2/PAC1 antagonist, pituitary adenylate cyclase activating peptide 6-38 (PACAP6-38) and the NOS inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME) were administered by intradermal microdialysis. PACAP6-38, L-NAME, a combination of PACAP6-38 and L-NAME, or Ringer's solution alone were perfused at four separate sites. Skin blood flow was monitored by laser-Doppler flowmetry at each site. Body temperature was controlled with water-perfused suits. Blood pressure was monitored by Finapres, and cutaneous vascular conductance (CVC) calculated (CVC = laser-Doppler flowmetry/mean arterial pressure). The protocol began with a 5- to 10-min baseline period without antagonist perfusion, followed by perfusion of PACAP6-38, L-NAME, or combined PACAP6-38 and L-NAME at the different sites in normothermia (45 min), followed by 3 min of whole body cooling. Whole body heating was then performed to induce heat stress and activate AVD. Finally, 58 mM sodium nitroprusside were perfused at all sites to effect maximal vasodilation for normalization of blood flow data. No significant differences in CVC (normalized to maximum) were found among Ringer's PACAP6-38, L-NAME, or combined antagonist sites during normothermia (P > 0.05 among sites) or cold stress (P > 0.05 among sites). CVC responses at all treated sites were attenuated during AVD (P < 0.05 vs. Ringer's). Attenuation was greater at L-NAME and combined PACAP6-38- and L-NAME-treated sites than at PACAP6-38 sites (P > 0.05). Because responses did not differ between L-NAME and combined treatment sites (P > 0.05), we conclude that VPAC2/PAC1 receptors require NO in series to effect AVD. C1 [Kellogg, Dean L., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr & Gerontol, Dept Med, San Antonio, TX 78229 USA. [Kellogg, Dean L., Jr.] Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Dept Vet Affairs, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Kellogg, Dean L., Jr.; Zhao, Joan L.; Wu, Yubo; Johnson, John M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. RP Kellogg, DL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr & Gerontol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kelloggd@uthscsa.edu NR 48 TC 9 Z9 10 U1 3 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2012 VL 113 IS 10 BP 1512 EP 1518 DI 10.1152/japplphysiol.00859.2012 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 038XZ UT WOS:000311208700002 PM 22961270 ER PT J AU Bradfield, J Shapiro, S Finch, W Tung, R Boyle, NG Buch, E Mathuria, N Mandapati, R Shivkumar, K Bersohn, M AF Bradfield, Jason Shapiro, Shelley Finch, William Tung, Roderick Boyle, Noel G. Buch, Eric Mathuria, Nilesh Mandapati, Ravi Shivkumar, Kalyanam Bersohn, Malcolm TI Catheter Ablation of Typical Atrial Flutter in Severe Pulmonary Hypertension SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial flutter; catheter ablation; cardiac hypertrophy; pulmonary hypertension AB Atrial Flutter and Pulmonary Hypertension. Background: Radiofrequency ablation is first-line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH). Methods: Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded. Results: A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 +/- 12 years. SPAP prior to ablation was 99 +/- 35 mmHg. Baseline 6-minute walk distance was 295 +/- 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 +/- 53 ms vs 252 +/- 35 ms, P = 0.006). Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 +/- 44 mmHg to 82 +/- 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 +/- 832 pg/mL vs 522 +/- 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year. Conclusion: Ablation of AFL in severe PAH patients is feasible, with good short- and intermediate-term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1-year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population. (J Cardiovasc Electrophysiol, Vol. 23, pp. 11851190, November 2012) C1 [Bradfield, Jason; Finch, William; Tung, Roderick; Boyle, Noel G.; Buch, Eric; Mathuria, Nilesh; Mandapati, Ravi; Shivkumar, Kalyanam; Bersohn, Malcolm] Univ Calif Los Angeles, David Geffen Sch Med, Ronald Reagan UCLA Med Ctr, UCLA Cardiac Arrhythmia Ctr, Los Angeles, CA 90095 USA. [Shapiro, Shelley; Bersohn, Malcolm] VA Greater Los Angeles Med Ctr, Los Angeles, CA USA. RP Bradfield, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ronald Reagan UCLA Med Ctr, UCLA Cardiac Arrhythmia Ctr, A2-237 CHS,650 Charles E Young Dr S, Los Angeles, CA 90095 USA. EM JBradfield@mednet.ucla.edu OI Shivkumar, Kalyanam/0000-0002-4121-1766 NR 9 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD NOV PY 2012 VL 23 IS 11 BP 1185 EP 1190 DI 10.1111/j.1540-8167.2012.02387.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 037HL UT WOS:000311092700006 PM 22734591 ER PT J AU Bredella, MA Lin, E Gerweck, AV Landa, MG Thomas, BJ Torriani, M Bouxsein, ML Miller, KK AF Bredella, Miriam A. Lin, Eleanor Gerweck, Anu V. Landa, Melissa G. Thomas, Bijoy J. Torriani, Martin Bouxsein, Mary L. Miller, Karen K. TI Determinants of Bone Microarchitecture and Mechanical Properties in Obese Men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE DEFICIENCY; CARDIOVASCULAR RISK; VISCERAL FAT; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; MARROW FAT; OSTEOPOROSIS; FRACTURE; IGF-1; PREVALENCE AB Context: Recent studies have suggested that obesity in men is associated with increased fracture risk. Obesity in men is also associated with dysregulation of the GH/IGF-I and gonadal steroid axes, important regulators of bone homeostasis. Objective: The aim of the study was to investigate body composition and endocrine determinants of bone microarchitecture and mechanical properties in obese men. Design and Setting: We conducted a cross-sectional study at a clinical research center. Participants: Thirty-five obese men (mean age, 33.8 +/- 6.4 yr; mean body mass index, 36.5 +/- 5.8 kg/m(2)) participated in the study. Outcome Measures: Distal radius microarchitecture and mechanical properties were measured by three-dimensional high-resolution peripheral quantitative computed tomography and microfinite element analysis; body composition by computed tomography; bone marrow fat by proton magnetic resonance spectroscopy; total and free estradiol and testosterone; IGF-I; peak glucagon-stimulated GH; 25-hydroxyvitamin D. Results: Men with high visceral adipose tissue (VAT) had impaired mechanical properties compared to men with low VAT (P < 0.05), despite comparable body mass index. VAT was inversely associated and thigh muscle was positively associated with mechanical properties (P < 0.05). Bone marrow fat was inversely associated with cortical parameters (P <= 0.02). Free estradiol was positively associated with total density (P = 0.05). Free testosterone was positively associated with trabecular thickness and inversely with trabecular number (P < 0.05). Peak stimulated GH was positively associated with trabecular thickness, as was IGF-I with cortical area (P <= 0.04). Conclusion: VAT and bone marrow fat are negative predictors and muscle mass is a positive predictor of microarchitecture and mechanical properties in obese men. Testosterone, estradiol, and GH are positive determinants of trabecular microarchitecture, and IGF-I is a positive determinant of cortical microarchitecture. This supports the notion that VAT is detrimental to bone and that decreased GH and testosterone, characteristic of male obesity, may exert deleterious effects on microarchitecture, whereas higher estradiol may be protective. (J Clin Endocrinol Metab 97: 4115-4122, 2012) C1 [Bredella, Miriam A.; Thomas, Bijoy J.; Torriani, Martin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lin, Eleanor; Gerweck, Anu V.; Landa, Melissa G.; Torriani, Martin; Miller, Karen K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Bouxsein, Mary L.] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [R01 HL-077674, UL1 RR-025758, K23 RR-23090] FX This work was supported in part by National Institutes of Health Grants R01 HL-077674, UL1 RR-025758, and K23 RR-23090. NR 40 TC 41 Z9 43 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP 4115 EP 4122 DI 10.1210/jc.2012-2246 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500061 PM 22933540 ER PT J AU Shaw, ND Butler, JP McKinney, SM Nelson, SA Ellenbogen, JM Hall, JE AF Shaw, N. D. Butler, J. P. McKinney, S. M. Nelson, S. A. Ellenbogen, J. M. Hall, J. E. TI Insights into Puberty: The Relationship between Sleep Stages and Pulsatile LH Secretion SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; GROWTH-HORMONE; DEVELOPMENTAL-CHANGES; RAT HYPOTHALAMUS; DIURNAL RHYTHMS; MESSENGER-RNA; NORMAL MEN; IN-VIVO AB Context: During the pubertal transition, LH secretion initially increases only during sleep; however, its relationship to sleep stage is unknown. Objectives: Our objective was to determine whether the initiation of LH pulses is related to a specific sleep stage in pubertal children. Design and Setting: Frequent blood sampling and polysomnographic studies were performed in a Clinical Research Center. Subjects: Fourteen studies were performed in nine healthy pubertal children, ages 9.9-15.6 yr. Interventions: Subjects underwent one to two overnight studies with polysomnography and blood sampling for LH at 10-min intervals. Results: Alignment of polysomnographic records and LH pulses demonstrated that LH pulses (n = 58) occurred most frequently during slow-wave sleep (SWS) (1.1 pulse/h, n = 30) compared with all other sleep stages or periods of wake after sleep onset (P < 0.001). There was also a significant increase in the amount of SWS in the 15 min preceding and the 5 min following each pulse compared with the amount of SWS seen across the study night (P < 0.01). Conclusions: During puberty, the majority of LH pulses that occur after sleep onset are preceded by SWS, suggesting that SWS is intimately involved in the complex control of pubertal onset. These studies raise concerns about the potential hormonal repercussions of the increasing prevalence of sleep disturbances in adolescents. (J Clin Endocrinol Metab 97: E2055-E2062, 2012) C1 [Shaw, N. D.; Hall, J. E.] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [McKinney, S. M.; Ellenbogen, J. M.] Massachusetts Gen Hosp, Sleep Div, Dept Med, Boston, MA 02114 USA. [Nelson, S. A.] Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. [Shaw, N. D.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Butler, J. P.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Butler, J. P.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Shaw, N. D.; Ellenbogen, J. M.; Hall, J. E.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA 02115 USA. RP Shaw, ND (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5,55 Fruit St, Boston, MA 02114 USA. EM nshaw@partners.org OI Shaw, Natalie/0000-0002-0847-9170 FU National Institutes of Health [5T32 HD062315]; Charles A. King Trust, Genentech; Pediatric Endocrine Society; American Medical Association; Thrasher Research Fund; Endocrine Fellows Foundation; Scholars in Clinical Science Program of Harvard Catalyst (The Harvard Clinical and Translational Science Center Award) [UL1 RR 025758]; Harvard University FX N.D.S. received fellowship support from the National Institutes of Health (5T32 HD062315), the Charles A. King Trust, Genentech, the Pediatric Endocrine Society, the American Medical Association, the Thrasher Research Fund, the Endocrine Fellows Foundation, and the Scholars in Clinical Science Program of Harvard Catalyst (The Harvard Clinical and Translational Science Center Award UL1 RR 025758), and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, the National Center for Research Resources, or the National Institutes of Health. NR 56 TC 9 Z9 9 U1 1 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2012 VL 97 IS 11 BP E2055 EP E2062 DI 10.1210/jc.2012-2692 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 032IT UT WOS:000310710500003 PM 22948756 ER PT J AU Magnani, JW Newton-Cheh, C O'Donnell, CJ Levy, D AF Magnani, Jared W. Newton-Cheh, Christopher O'Donnell, Christopher J. Levy, Daniel TI Development and application of a longitudinal electrocardiogram repository: the Framingham Heart Study SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Electrocardiography; Epidemiology; Repository; Framingham ID CHRONIC ATRIAL-FIBRILLATION AB The electrocardiogram (ECG) has widespread use in clinical care and research. Despite its extensive use and study, important gaps remain in examining prospective, repeated longitudinal ECG measures, and their association with cardiovascular outcomes. The Framingham Heart Study (FRS) is a community-based study designed to examine risk factors and outcomes associated with cardiovascular disease. Here, we describe a novel effort in the FHS to develop a unique resource: serial ECGs conducted on 3 generations of study participants spanning multiple decades (1986 to the present). We describe the FHS and the role the ECG has had in conducting cardiovascular epidemiology in the FHS. We then describe potential applications for a longitudinal ECG repository. We expect the Framingham ECG repository to enhance cardiovascular research and epidemiologic study. Such a resource will complement the phenotypic and genotypic characterization of FHS, facilitating novel investigations of cardiovascular epidemiology. (C) 2012 Elsevier Inc. All rights reserved. C1 [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, Boston, MA 02118 USA. [Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Newton-Cheh, Christopher; O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Magnani, Jared W.; Newton-Cheh, Christopher; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham, MA USA. [O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. RP Magnani, JW (reprint author), Boston Univ, Sch Med, Sect Cardiovasc Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jmagnani@bu.edu FU National Institutes of Health (NIH) [R21HL106092]; American Heart Association [09FTF219028]; NIH [6R01-NS17950, N01-HC25195] FX Dr Magnani is supported by grants from the National Institutes of Health (NIH) (R21HL106092) and the American Heart Association (09FTF219028). This work was supported by NIH grants 6R01-NS17950, N01-HC25195. NR 13 TC 3 Z9 3 U1 0 U2 6 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 673 EP 676 DI 10.1016/j.jelectrocard.2012.06.016 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300026 PM 22832152 ER PT J AU Ofman, P Cook, JR Navaravong, L Levine, RA Peralta, A Gaziano, JM Djousse, L Curillova, Z Hoffmeister, P Smoot, K Jiang, L Tighe, DA Stoenescu, ML AF Ofman, Peter Cook, James R. Navaravong, Leenhapong Levine, Robert A. Peralta, Adelqui Gaziano, J. Michael Djousse, Luc Curillova, Zelmira Hoffmeister, Peter Smoot, Kyle Jiang, Leng Tighe, Dennis A. Stoenescu, Mathias L. TI T-wave inversion and diastolic dysfunction in patients with electrocardiographic left ventricular hypertrophy SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE T-wave inversion; Diastolic dysfunction; Left ventricular hypertrophy ID PRESERVED EJECTION FRACTION; SOCIETY-OF-CARDIOLOGY; HEART-FAILURE; HYPERTENSIVE PATIENTS; STRAIN PATTERN; REPOLARIZATION; ECHOCARDIOGRAPHY; RECOMMENDATIONS; DIAGNOSIS; LIFE AB Objectives: The aim of this study was to investigate if T-wave inversion (TWI) in the settings of electrocardiogram (ECG)-left ventricular hypertrophy (LVH) is associated with advanced diastolic dysfunction (DD) in subjects with preserved ejection fraction (EF). Background: Animal studies suggested that an abnormal transmural repolarization sequence from endocardium to epicardium may contribute to DD. However, little is known about abnormal repolarization sequence and DD in humans. Methods: We studied 231 patients with ECG-diagnosed LVH and with an EF of 50% or greater (measured within 6 months of the index ECG). T-wave inversion was assessed on leads I, aVL, V-4, V-5, or V-6. Diastolic dysfunction was defined based on echocardiographic estimation of the left atrial pressure. We used multiple logistic regression to estimate the odds ratio of DD comparing patients with TWI with those without TWI. Results: The average age was 65.0 +/- 14.2 years, and 61% were women. The mean EF was 61.8% +/- 6.6%. Patients with TWIs were more likely to have coronary artery disease (P = .013) and diabetes (P = .007). There was a 5.6-fold increased odds of DD in patients with TWI compared with those without TWI in a model adjusting for sex, age, relative wall thickness, body mass index, hypertension, coronary artery disease, diabetes, hyperlipidemia, and smoking. When comparing different echocardiographic estimates of the left atrial pressure, patients with TWI displayed higher values for septal and lateral E/e', left atrial volume index, and right ventricular/right atrial peak systolic gradient (P < .01 for each parameter). Conclusions: T-wave inversion is associated with increased odds of DD in patients with ECG-LVH with preserved systolic function. The reversal of the normal sequence of repolarization manifested on the 12-lead ECG as TWI may be a factor to DD. Published by Elsevier Inc. C1 [Ofman, Peter; Peralta, Adelqui; Gaziano, J. Michael; Curillova, Zelmira; Hoffmeister, Peter] VA Boston Healthcare Syst, Div Cardiol, Boston, MA 02132 USA. [Ofman, Peter; Levine, Robert A.; Peralta, Adelqui; Gaziano, J. Michael; Djousse, Luc; Curillova, Zelmira; Hoffmeister, Peter] Harvard Univ, Sch Med, Boston, MA USA. [Ofman, Peter; Cook, James R.; Navaravong, Leenhapong; Jiang, Leng; Stoenescu, Mathias L.] Tufts Univ, Sch Med, Springfield, MA 01199 USA. [Ofman, Peter; Cook, James R.; Navaravong, Leenhapong; Jiang, Leng; Stoenescu, Mathias L.] Baystate Med Ctr, Div Cardiol, Springfield, MA USA. [Ofman, Peter; Gaziano, J. Michael; Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA. [Levine, Robert A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gaziano, J. Michael; Djousse, Luc; Smoot, Kyle] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA. [Gaziano, J. Michael; Djousse, Luc; Smoot, Kyle] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Tighe, Dennis A.] Univ Massachusetts, Med Ctr, Div Cardiol, Worcester, MA USA. RP Ofman, P (reprint author), VA Boston Healthcare Syst, Div Cardiol, 1400 VFW Pkwy, Boston, MA 02132 USA. EM Peter.Ofman@va.gov RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 21 TC 1 Z9 1 U1 1 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD NOV-DEC PY 2012 VL 45 IS 6 BP 764 EP 769 DI 10.1016/j.jelectrocard.2012.06.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 032ZZ UT WOS:000310763300043 PM 22819483 ER PT J AU Baggett, TP Anderson, R Freyder, PJ Jarvie, JA Maryman, K Porter, J Rigotti, NA AF Baggett, Travis P. Anderson, Robert Freyder, Paul J. Jarvie, Jill A. Maryman, Kristi Porter, Janet Rigotti, Nancy A. TI Addressing Tobacco Use in Homeless Populations: A Survey of Health Care Professionals SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Homeless persons (MeSH); tobacco use cessation (MeSH); directive counseling (MeSH); attitude of health personnel (MeSH) ID CIGARETTE-SMOKING; RISK-FACTORS; ADULTS; CESSATION; BEHAVIOR; DISEASE AB Cigarette smoking is common among homeless individuals, but little is known about health care providers' practices and attitudes in addressing tobacco use in this vulnerable population. We surveyed members of the Health Care for the Homeless Clinicians' Network, a nationwide multidisciplinary organization, to assess their tobacco screening practices, attitudes toward addressing tobacco use, and experience providing tobacco products to homeless individuals. Of 231 clinicians who completed the survey, 86.5% reported routinely screening for tobacco use. Although 74.4% of respondents viewed tobacco use as one of the most important health issues among homeless people, rates of agreement with this and other attitudes toward tobacco use in the setting of homelessness varied significantly by clinical discipline. Overall, 15.3% of respondents reported having ever given patients tobacco to build trust or promote adherence to care. Addressing providers' attitudinal variations and tobacco distribution practices may foster a more consistent anti-smoking message for this population. C1 [Baggett, Travis P.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Baggett, Travis P.] Boston Hlth Care Homeless Program, Boston, MA USA. [Anderson, Robert] W Virginia Univ, Sch Publ Hlth, Translat Tobacco Reduct Res Program, Prevent Res Ctr, Morgantown, WV 26506 USA. [Freyder, Paul J.] Salvat Army Harbor Light Ctr, Pittsburgh, PA USA. [Jarvie, Jill A.] Kaiser Fdn Hosp, San Rafael, CA USA. [Maryman, Kristi; Porter, Janet] Hlth Educ Council, W Sacramento, CA USA. [Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Baggett, TP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM tbaggett@partners.org FU NCCDPHP CDC HHS [1U58DP001518, U48DP001921]; NHLBI NIH HHS [K24-HL04440] NR 21 TC 11 Z9 11 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2012 VL 23 IS 4 BP 1650 EP 1659 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 036CF UT WOS:000311003300027 PM 23698679 ER PT J AU Nghiemphu, PL Lai, A Green, RM Reardon, DA Cloughesy, T AF Nghiemphu, Phioanh Leia Lai, Albert Green, Richard M. Reardon, David A. Cloughesy, Timothy TI A dose escalation trial for the combination of erlotinib and sirolimus for recurrent malignant gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Erlotinib; Sirolimus; Recurrent gliomas; Combination study ID GROWTH-FACTOR RECEPTOR; EGFR KINASE INHIBITORS; LUNG-CANCER; TUMOR-CELLS; GLIOBLASTOMA; EXPRESSION; AMPLIFICATION; THERAPIES; GENE AB In order to achieve higher dosages than previously used in clinical trials, we conducted a phase I trial to determine the maximum tolerated dose (MTD) for the combination of erlotinib and sirolimus for the treatments of recurrent malignant gliomas. Patients with pathologically proven World Health Organization (WHO) grade III glioma and grade IV glioblastoma and radiographically proven tumor recurrence were eligible for this study. Treatments included once daily erlotinib, which was given alone for the first 7 days of treatments, then in combination with once daily sirolimus. Sirolimus was given with a loading dose on day 8 followed by a maintenance dose starting on day 9. Dose-limiting toxicity (DLT) was determined over the first 28 days of treatments, and the MTD was determined in a 3 + 3 classic study design. 19 patients were enrolled, and 13 patients were eligible for MTD determination. The MTD was determined to be 150 mg daily for erlotinib and 5 mg daily (after a 15 mg loading dose) for sirolimus. The DLTs included rash and mucositis (despite maximal medical managements), hypophosphatemia, altered mental status, and neutropenia. The combination of erlotinib and sirolimus is difficult to tolerate at dosages higher than previously reported in phase II trials. C1 [Nghiemphu, Phioanh Leia; Lai, Albert; Cloughesy, Timothy] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90230 USA. [Green, Richard M.] Kaiser Permanente, Dept Neurol, Los Angeles, CA USA. [Reardon, David A.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. RP Nghiemphu, PL (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza,Reed 1-230, Los Angeles, CA 90230 USA. EM leian@ucla.edu FU Genentech, Inc. FX A.L. received research funding from Genentech, Inc. T.C. received honoraria from Genentech, Inc. NR 26 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2012 VL 110 IS 2 BP 245 EP 250 DI 10.1007/s11060-012-0960-y PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 038XT UT WOS:000311208100011 PM 22918789 ER PT J AU Kobus, AM Smith, DH Morasco, BJ Johnson, ES Yang, XH Petrik, AF Deyo, RA AF Kobus, Amy M. Smith, David H. Morasco, Benjamin J. Johnson, Eric S. Yang, Xiuhai Petrik, Amanda F. Deyo, Richard A. TI Correlates of Higher-Dose Opioid Medication Use for Low Back Pain in Primary Care SO JOURNAL OF PAIN LA English DT Article DE Chronic pain; back pain; opioids; epidemiology; pain/drug therapy ID CHRONIC NONCANCER PAIN; MENTAL-HEALTH DISORDERS; SUBSTANCE USE DISORDERS; PRESCRIBED OPIOIDS; ASSOCIATION; RISK; GUIDELINE; OVERDOSE; TRENDS AB Factors associated with high-dose opioid therapy for noncancer pain are poorly understood. We documented the prevalence of high-dose opioid use as well as associated demographic, clinical, and health service utilization correlates among low back pain patients. Patients prescribed higher doses of opioids (>= 100 mg/day morphine equivalent at last dispensing; n = 453) and receiving opioids for 90+ consecutive days were compared to 2 groups: lower-dose opioid group (1-99 mg/day; n = 4,815) or no-opioid group (n = 10,184). Higher-dose opioid use occurred in 2.9% of patients who received any opioids and in 8.6% of patients who received opioids long-term. The median dose in the higher-dose group was 180.0 mg/day. Compared to the no-opioid group, higher-dose users reported poorer health. Compared to either comparison group, patients in the higher-dose group had higher rates of mental health and substance use disorders, concurrent sedative-hypnotic use (60.5%; n = 274), and health service utilization. After adjusting for select covariates, male gender (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.37-2.06), higher comorbidity, Medicare coverage (OR = 1.65, 95% CI = 1.22-2.23), any mental health or substance use diagnosis (OR = 1.58, 95% CI = 1.28-1.95), co-prescriptions of sedative-hypnotics (OR = 1.75, 95% CI = 1.42-2.16), and more emergency department and specialty pain clinic visits were associated with higher likelihood of high-dose prescriptions. Perspective: Higher-dose opioid therapy is being prescribed to 8.6% of back pain patients who receive long-term opioids. These patients had higher mental health and medical comorbidities and co-prescriptions of sedative-hypnotics, raising potential safety concerns. (C) 2012 by the American Pain Society. Published by Elsevier Inc. All rights reserved C1 [Kobus, Amy M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97239 USA. [Smith, David H.; Johnson, Eric S.; Yang, Xiuhai; Petrik, Amanda F.; Deyo, Richard A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Morasco, Benjamin J.] Portland VA Med Ctr, Portland, OR USA. RP Kobus, AM (reprint author), Oregon Hlth & Sci Univ, Dept Psychiat, Mail Code OP 02,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM kobusa@ohsu.edu FU Agency of Healthcare Research and Quality [5T32HSO17582]; Oregon Clinical and Translational Research Institute; National Center for Research Resource, National Institutes of Health [UL1 RR024140]; National Institutes of Health Roadmap for Medical Research FX This study was supported in part by an NRSAT32 Fellowship in Health Services Research from the Agency of Healthcare Research and Quality to Dr. Kobus (5T32HSO17582) and a pilot grant from the Oregon Clinical and Translational Research Institute, grant number UL1 RR024140 from the National Center for Research Resources, National Institutes of Health; and the National Institutes of Health Roadmap for Medical Research. NR 33 TC 23 Z9 23 U1 0 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD NOV PY 2012 VL 13 IS 11 BP 1131 EP 1138 DI 10.1016/j.jpain.2012.09.003 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 038MT UT WOS:000311179500010 PM 23117108 ER PT J AU Bailey, FA Williams, BR Goode, PS Woodby, LL Redden, DT Johnson, TM Taylor, JW Burgio, KL AF Bailey, F. Amos Williams, Beverly R. Goode, Patricia S. Woodby, Lesa L. Redden, David T. Johnson, Theodore M., II Taylor, Janice W. Burgio, Kathryn L. TI Opioid Pain Medication Orders and Administration in the Last Days of Life SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE End of life; pain; hospice; inpatient; palliative care; opioids ID INTENSIVE-CARE-UNIT; OF-LIFE; HOSPICE CARE; HOSPITALIZED-PATIENTS; PALLIATIVE CARE; IMPROVE CARE; ILL PATIENTS; END; CANCER; QUALITY AB Context. Most patients with serious and life-limiting illness experience pain at some point in the illness trajectory. Objectives. To describe baseline pain management practices for imminently dying patients in Veterans Administration Medical Centers (VAMCs) and examine factors associated with these processes, including presence of opioid orders at the time of death and medication administration in the last seven days, 48 hours, and 24 hours of life. Methods. Data on orders and administration of opioid pain medication at the end of life were abstracted from the medical records of veterans who died in six VAMC hospitals in 2005. Results. Of 1068 patient records, 686 (64.2%) had an active order for an opioid medication at the time of death. Of these, 69.8% of patients had received the medication at some time within the last seven days of life, 61.2% within the last 48 hours, and 47.0% within the last 24 hours. In multivariable models, presence of an order for opioid pain medication at the time of death and administration within the last 24 hours were both significantly associated with having a Do Not Resuscitate (DNR) order (P < 0.0001/0.0002), terminal condition (P < 0.0001/< 0.0001), family presence (P < 0.0001/0.0023), location of death (P = 0.003/0.0005), and having pain noted in the care plan (P = 0.0073/0.0007). Conclusion. Findings indicate a need for improving availability of opioids for end-of-life care in the inpatient setting. Modifiable factors, such as family presence and goals-of-care discussions, suggest potential targets for intervention to improve recognition of the dying process and proactive planning for pain control. J Pain Symptom Manage 2012; 44: 681-691. Published by Elsevier Inc. on behalf of U.S. Cancer Pain Relief Committee. C1 [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Redden, David T.; Johnson, Theodore M., II; Taylor, Janice W.; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Dept Vet Affairs, Birmingham, AL USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Redden, David T.; Johnson, Theodore M., II; Taylor, Janice W.; Burgio, Kathryn L.] Birmingham Atlanta Geriatr Res Educ & Clin Ctr GR, Dept Vet Affairs, Atlanta, GA USA. [Bailey, F. Amos; Williams, Beverly R.; Goode, Patricia S.; Woodby, Lesa L.; Redden, David T.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL USA. [Johnson, Theodore M., II] Emory Univ, Atlanta, GA 30322 USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, Geriatr Res Educ & Clin Ctr, 11G,700 S 19th St, Birmingham, AL 35233 USA. EM kburgio@aging.uab.edu FU Department of Veterans Affairs, VHA, Health Services Research and Development Service [IIR 03-126] FX This research was supported by a Merit Review grant from the Department of Veterans Affairs, VHA, Health Services Research and Development Service (IIR 03-126; K. L. B., principal investigator; F. A. B., co-principal investigator). The funding source had no role in the collection, analysis, interpretation, or presentation of the information contained in this article. The authors do not perceive any conflicts of interest related to the research reported in this article. NR 52 TC 4 Z9 4 U1 0 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2012 VL 44 IS 5 BP 681 EP 691 DI 10.1016/j.jpainsymman.2011.11.006 PG 11 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 043TB UT WOS:000311570400007 PM 22765968 ER PT J AU Imamura, M Ozcakar, L Fregni, F Hsing, WT Battistella, LR AF Imamura, Marta Ozcakar, Levent Fregni, Felipe Hsing, Wu Tu Battistella, Linamara Rizzo TI EXPLORING A LONG-TERM GLOBAL APPROACH FOR MUSCULOSKELETAL ULTRASOUND TRAINING: WORLD-MUSCULUS SO JOURNAL OF REHABILITATION MEDICINE LA English DT Letter ID REHABILITATION-MEDICINE; ULTRASONOGRAPHY; SONOGRAPHY C1 [Imamura, Marta; Battistella, Linamara Rizzo] Univ Sao Paulo, Sch Med, Inst Phys & Rehabil Med, Sao Paulo, Brazil. [Ozcakar, Levent] Hacettepe Univ, Sch Med, Dept Phys Med & Rehabil, Ankara, Turkey. [Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Lab Neuromodulat, Boston, MA USA. [Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Ctr Clin Res Learning, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Hsing, Wu Tu] Univ Sao Paulo, Sch Med, Dept Telemed, Sao Paulo, Brazil. RP Imamura, M (reprint author), Univ Sao Paulo, Sch Med, Inst Phys & Rehabil Med, Sao Paulo, Brazil. EM marta.imamura@redelucymontoro.org.br RI Battistella, Linamara /E-5131-2013; Imamura, Marta/M-8249-2013; Hsing, Wu Tu/C-3004-2014 NR 10 TC 2 Z9 2 U1 0 U2 2 PU FOUNDATION REHABILITATION INFORMATION PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 1650-1977 J9 J REHABIL MED JI J. Rehabil. Med. PD NOV PY 2012 VL 44 IS 11 BP 991 EP 992 DI 10.2340/16501977-1080 PG 2 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 036VW UT WOS:000311061400016 PM 23069862 ER PT J AU Dewhurst, C Rosen, MP Blake, MA Baker, ME Cash, BD Fidler, JL Greene, FL Hindman, NM Jones, B Katz, DS Lalani, T Miller, FH Small, WC Sudakoff, GS Tulchinsky, M Yaghmai, V Yee, J AF Dewhurst, Catherine Rosen, Max P. Blake, Michael A. Baker, Mark E. Cash, Brooks D. Fidler, Jeff L. Greene, Frederick L. Hindman, Nicole M. Jones, Bronwyn Katz, Douglas S. Lalani, Tasneem Miller, Frank H. Small, William C. Sudakoff, Gary S. Tulchinsky, Mark Yaghmai, Vahid Yee, Judy TI ACR Appropriateness Criteria (R) Pretreatment Staging of Colorectal Cancer SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; colorectal neoplasms; tumor staging; computed tomography; magnetic resonance imaging; ultrasound ID ADVANCED RECTAL-CANCER; POSITRON-EMISSION-TOMOGRAPHY; BODY PET/CT-COLONOGRAPHY; DIFFUSION-WEIGHTED MRI; COMPUTED-TOMOGRAPHY; ENDORECTAL ULTRASOUND; RADIATION-THERAPY; CT COLONOGRAPHY; CIRCUMFERENTIAL MARGIN; DIAGNOSTIC-ACCURACY AB Because virtually all patients with colonic cancer will undergo some form of surgical therapy, the role of preoperative imaging is directed at determining the presence or absence of synchronous carcinomas or adenomas and local or distant metastases. In contrast, preoperative staging for rectal carcinoma has significant therapeutic implications and will direct the use of radiation therapy, surgical excision, or chemotherapy. CT of the chest, abdomen, and pelvis is recommended for the initial evaluation for the preoperative assessment of patients with colorectal carcinoma. Although the overall accuracy of CT varies direcdy with the stage of colorectal carcinoma, CT can accurately assess the presence of metastatic disease. MRI using endorectal coils can accurately assess the depth of bowel wall penetration of rectal carcinomas. Phased-array coils provide additional information about lymph node involvement. Adding diffusion-weighted imaging to conventional MRI yields better diagnostic accuracy than conventional MRI alone. Transrectal ultrasound can distinguish layers within the rectal wall and provides accurate assessment of the depth of tumor penetration and perirectal spread, and PET and PET/CT have been shown to alter therapy in almost one-third of patients with advanced primary rectal cancer. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Dewhurst, Catherine; Rosen, Max P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Blake, Michael A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin, Cleveland, OH 44106 USA. [Cash, Brooks D.] Natl Naval Med Ctr, Bethesda, MD USA. [Cash, Brooks D.] Amer Gastroenterol Assoc, Bethesda, MD USA. [Fidler, Jeff L.] Mayo Clin, Rochester, MN USA. [Greene, Frederick L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Greene, Frederick L.] Amer Coll Surg, Chicago, IL USA. [Hindman, Nicole M.] NYU, Med Ctr, New York, NY 10016 USA. [Jones, Bronwyn] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Katz, Douglas S.] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Lalani, Tasneem] Inland Imaging Associates, Seattle, WA USA. [Lalani, Tasneem] Univ Washington, Seattle, WA 98195 USA. [Miller, Frank H.] Northwestern Univ, Feinberg Sch Med NMH, Chicago, IL 60611 USA. [Small, William C.] Emory Univ, Atlanta, GA 30322 USA. [Sudakoff, Gary S.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Tulchinsky, Mark] Milton S Hershey Med Ctr, Hershey, PA USA. [Tulchinsky, Mark] Soc Nucl Med & Mol Imaging, Reston, VA USA. [Yee, Judy] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Rosen, MP (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM max.rosen@umassmemorial.org FU Siemens Healthcare FX Max P. Rosen, MD, MPH, is a stock holder of Anvita Health; Mark E. Baker, MD, reported a research agreement with Siemens Healthcare (hardware; software), monetary support for research forthcoming (agreement not signed). NR 63 TC 27 Z9 28 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2012 VL 9 IS 11 BP 775 EP 781 DI 10.1016/j.jacr.2012.07.025 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 038QL UT WOS:000311189100007 PM 23122343 ER PT J AU Morrison, LK Siddiqi, AU Roberts, WC Lee, J Saini, S Thrall, JH AF Morrison, Lai Kuen Siddiqi, Assad U. Roberts, Whitney C. Lee, Jae Saini, Sanjay Thrall, James H. TI A Collaborative Capital Planning Process for Departments of Radiology SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Morrison, Lai Kuen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Morrison, LK (reprint author), Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St, Boston, MA 02114 USA. EM lmorrison1@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD NOV PY 2012 VL 9 IS 11 BP 839 EP 843 DI 10.1016/j.jacr.2012.05.018 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 038QL UT WOS:000311189100018 PM 23122354 ER PT J AU Pugh, MJV Copeland, LA Zeber, JE Wang, CP Amuan, ME Mortensen, EM Tabares, JV Van Cott, AC Cooper, TL Cramer, JA AF Pugh, Mary Jo V. Copeland, Laurel A. Zeber, John E. Wang, Chen-Pin Amuan, Megan E. Mortensen, Eric M. Tabares, Jeffrey V. Van Cott, Anne C. Cooper, Toby L. Cramer, Joyce A. TI Antiepileptic Drug Monotherapy Exposure and Suicide-Related Behavior in Older Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE suicide; epidemiology; psychiatric disorders; antiepileptic drugs; geriatrics ID NEW-ONSET EPILEPSY; PROPENSITY SCORES; BIPOLAR DISORDER; FDA ALERT; RISK; POPULATION; INDIVIDUALS; DIVALPROEX; DEPRESSION; LITHIUM AB Objectives To examine the association between antiepileptic drug (AED) receipt and suicide-related behavior (SRB) in older veterans. Design Retrospective database analysis. Setting Veterans Health Administration (VHA) inpatient and outpatient care. Participants Veterans aged 65 and older in 2004 to 2006. Measurements SRB was identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes, and new AED monotherapy was identified using the VHA product variable in pharmacy data. Comorbid conditions and medications were also identified as potential confounders using previously validated algorithms. Cox proportional hazards models controlling for the propensity to receive AEDs examined the association between any AED exposure, specific AEDs, and time to SRB. Results Within the eligible sample of 2.15 million individuals, 332 cases of SRB were found. Overall, 98% of participants were male, and 67% were non-Hispanic white. Affective disorders and severe psychiatric conditions were strongly associated with SRB and were included in the propensity score. AED exposure displayed a significant association with SRB (odds ratio = 4.10, 95% confidence interval (CI) = 3.85-6.63) after adjusting for propensity to receive AEDs. Stratified analyses found similar results for those with (hazard ratio (HR) = 4.00, 95% CI = 2.9-5.5) and without (HR = 4.57, 95% CI = 1.15-18.20) mental health comorbidities. Gabapentin, phenytoin, lamotrigine, levetiracetam, topiramate, and valproate were significantly associated with SRB. Conclusion Exposure to five common AEDs was associated with SRB in older VHA beneficiaries. Given the strong associations between psychiatric comorbidity and SRB, clinicians treating elderly adults should weigh this potential adverse effect into their consideration for treatment of those receiving AEDs. Particular attention should be given to depression and suicidality screening in people prescribed AEDs. J Am Geriatr Soc 60: 2042-2047, 2012. C1 [Pugh, Mary Jo V.; Wang, Chen-Pin; Tabares, Jeffrey V.] S Texas Vet Hlth Care Syst VERDICT, San Antonio, TX USA. [Pugh, Mary Jo V.; Wang, Chen-Pin] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Copeland, Laurel A.; Zeber, John E.] Cent Texas Vet Hlth Care Syst, Temple, TX USA. [Copeland, Laurel A.; Zeber, John E.] Scott & White Healthcare, Ctr Appl Hlth Res, Temple, TX USA. [Amuan, Megan E.] Edith Nourse Rogers Mem Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Mortensen, Eric M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Gen Med, San Antonio, TX 78229 USA. [Mortensen, Eric M.] S Texas Vet Hlth Care Syst, Div Gen Internal Med, San Antonio, TX 78229 USA. [Van Cott, Anne C.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Van Cott, Anne C.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Cooper, Toby L.] Carl R Darnall Army Med Ctr, Ft Hood, TX USA. [Cramer, Joyce A.] Yale Univ, Sch Med, New Haven, CT USA. [Cramer, Joyce A.] Epilepsy Therapy Project, Houston, TX USA. RP Pugh, MJV (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, VERDICT 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM pughm@uthscsa.edu OI Pugh, Mary Jo/0000-0003-4196-7763; Mortensen, Eric/0000-0002-3880-5563; Copeland, Laurel/0000-0002-9478-0209 FU VA Health Services Research and Development Service [IIR 06-062]; Central Texas, VA FX This study was funded by VA Health Services Research and Development Service Grant IIR 06-062 (Dr. Pugh, PI).; Laurel Copeland, and John Zeber receive salary from grants through their facility (Central Texas, VA); John Zeber is an editorial board member for the World Journal of Psychiatry, but receives no salary and declares no conflict with this manuscript. NR 42 TC 14 Z9 14 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2012 VL 60 IS 11 BP 2042 EP 2047 DI 10.1111/j.1532-5415.2012.04207.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 037LF UT WOS:000311105000006 PM 23110401 ER PT J AU Min, LL Shekelle, P AF Min, Lillian Shekelle, Paul TI Wanted: A FRAME for Staging Functional Decline in Older Adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID VULNERABLE ELDERS SURVEY; PEOPLE; COMMUNITY; FRAILTY C1 [Min, Lillian] Univ Michigan, Sch Med, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48105 USA. [Shekelle, Paul] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. [Shekelle, Paul] RAND Corp Hlth, Santa Monica, CA USA. RP Min, LL (reprint author), Univ Michigan, Sch Med, Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI 48105 USA. NR 7 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2012 VL 60 IS 11 BP 2167 EP 2168 DI 10.1111/j.1532-5415.2012.04215.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 037LF UT WOS:000311105000025 PM 23148420 ER PT J AU Semla, TP Fick, DM AF Semla, Todd P. Fick, Donna M. TI 2012 UPDATED BEERS CRITERIA: GREATER APPLICABILITY TO EUROPE? RESPONSE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Semla, Todd P.] US Dept Vet Affairs, Natl Pharm Benefits Management Serv, Hines, IL 60141 USA. [Semla, Todd P.] Northwestern Univ, Chicago, IL 60611 USA. [Fick, Donna M.] Penn State Univ, Sch Nursing, University Pk, PA 16802 USA. [Fick, Donna M.] Penn State Univ, Coll Med, University Pk, PA 16802 USA. RP Semla, TP (reprint author), US Dept Vet Affairs, Natl Pharm Benefits Management Serv, Hines, IL 60141 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2012 VL 60 IS 11 BP 2189 EP 2190 DI 10.1111/j.1532-5415.2012.04218.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 037LF UT WOS:000311105000041 ER PT J AU Semla, TP Fick, DM AF Semla, Todd P. Fick, Donna M. TI CREDULOUS FONDNESS FOR CELECOXIB RESPONSE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLO-OXYGENASE-2 INHIBITORS; BEERS CRITERIA; ULCER; RISK C1 [Semla, Todd P.] Northwestern Univ, US Dept Vet Affairs, Natl Pharm Benefits Management Serv, Chicago, IL 60611 USA. [Fick, Donna M.] Penn State Univ, Coll Med, Sch Nursing, University Pk, PA 16802 USA. RP Semla, TP (reprint author), Northwestern Univ, US Dept Vet Affairs, Natl Pharm Benefits Management Serv, Chicago, IL 60611 USA. NR 7 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2012 VL 60 IS 11 BP 2190 EP 2191 DI 10.1111/j.1532-5415.2012.04220.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 037LF UT WOS:000311105000043 ER PT J AU Yoshikawa, TT AF Yoshikawa, Thomas T. TI Reply to Response to Gerogeriatrics SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 [Yoshikawa, Thomas T.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Vet, Los Angeles, CA 90073 USA. [Yoshikawa, Thomas T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Yoshikawa, TT (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Vet, Los Angeles, CA 90073 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2012 VL 60 IS 11 BP 2192 EP 2192 DI 10.1111/j.1532-5415.2012.04221.x PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 037LF UT WOS:000311105000045 ER PT J AU Ackman, JB Mino-Kenudson, M Morse, CR AF Ackman, Jeanne B. Mino-Kenudson, Mari Morse, Christopher R. TI Nonsuppressing Normal Thymus on Chemical Shift Magnetic Resonance Imaging in a Young Woman SO JOURNAL OF THORACIC IMAGING LA English DT Editorial Material DE chemical shift magnetic resonance imaging; non-suppression; thymus; thymic hyperplasia; young women ID PREGNANCY AB A previously healthy 21-year-old woman presented with syncope and arrhythmia. A computed tomographic coronary angiogram was solely remarkable for an anterior mediastinal mass. Mediastinal magnetic resonance imaging of the reported mass revealed mildly prominent thymic tissue for age, with no suppression on out-of-phase chemical shift magnetic resonance imaging. Thymoma and lymphoma could not be excluded. After diagnosis and stabilization of her arrhythmia, the patient underwent median sternotomy and radical thymectomy, with pathology revealing normal thymus. This case suggests that nonsuppression of mildly prominent, homogenous thymic soft tissue in young women may not be sufficient to warrant diagnostic intervention and instead may warrant close follow-up. C1 [Ackman, Jeanne B.] Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Morse, Christopher R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Ackman, JB (reprint author), Massachusetts Gen Hosp, Div Thorac Radiol, Founders House 202,55 Fruit St, Boston, MA 02114 USA. EM jackman@partners.org NR 8 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2012 VL 27 IS 6 BP W196 EP W198 DI 10.1097/RTI.0b013e318249936a PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 028OT UT WOS:000310432600013 PM 22487991 ER PT J AU Tafti, BA Berenji, GR Santiago, S Barack, BM AF Tafti, Bashir Akhavan Berenji, Gholam R. Santiago, Silverio Barack, Bruce M. TI Contralateral Decubitus Positioning Enhances Computed Tomographic Angiographic Evaluation of Pulmonary Vasculature in a Patient With a Pulmonary Arteriovenous Malformation SO JOURNAL OF THORACIC IMAGING LA English DT Editorial Material DE pulmonary embolism; arteriovenous malformation; computed tomography angiography; pulmonary angiography; diagnostic pitfall ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; CT; CIRCULATION; EMBOLISM AB Computed tomographic pulmonary angiography has become the diagnostic procedure of choice in patients suspected of having a pulmonary embolus. However, intrapulmonary shunting of blood in a variety of pathologic conditions can cause suboptimal opacification of the pulmonary arterial circulation and result in a suboptimal or even nondiagnostic study. Radiologists should be aware of these conditions and be familiar with positioning techniques to minimize such shunting. We report a patient suspected of having pulmonary embolism, in whom a preexisting unilateral arteriovenous malformation prevented adequate evaluation of the pulmonary circulation. Positioning the patient in the contralateral decubitus position significantly enhanced image quality. C1 [Tafti, Bashir Akhavan; Berenji, Gholam R.; Barack, Bruce M.] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Imaging, Los Angeles, CA 90073 USA. [Santiago, Silverio] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Pulm & Crit Care, Los Angeles, CA 90073 USA. RP Barack, BM (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Dept Imaging, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Bruce.Barack@va.gov NR 10 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0883-5993 J9 J THORAC IMAG JI J. Thorac. Imaging PD NOV PY 2012 VL 27 IS 6 BP W193 EP W195 DI 10.1097/RTI.0b013e318242b4b3 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 028OT UT WOS:000310432600012 PM 22437510 ER PT J AU Hogan, MJ Marshalleck, FE Sidhu, MK Connolly, BL Towbin, RB Saad, WA Cahill, AM Crowley, J Heran, MKS Hohenwalter, EJ Roebuck, DJ Temple, MJ Walker, TG Cardella, JF AF Hogan, Mark J. Marshalleck, Francis E. Sidhu, Manrita K. Connolly, Bairbre L. Towbin, Richard B. Saad, Wael A. Cahill, Ann Marie Crowley, John Heran, Manraj K. S. Hohenwalter, Eric J. Roebuck, Derek J. Temple, Michael J. Walker, T. Gregory Cardella, John F. CA Soc Interventional Radiology Stand Soc Pediat Radiology Interventiona TI Quality Improvement Guidelines for Pediatric Abscess and Fluid Drainage SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material ID DEEP PELVIC ABSCESSES; ASSISTED THORACOSCOPIC SURGERY; GUIDED TRANSGLUTEAL DRAINAGE; INTERVENTIONAL RADIOLOGY; TRANSRECTAL DRAINAGE; COMPLICATED APPENDICITIS; INTRAABDOMINAL ABSCESSES; PERCUTANEOUS TREATMENT; LUNG ABSCESS; CHILDREN C1 [Hogan, Mark J.] Nationwide Childrens Hosp, Dept Radiol, Columbus, OH USA. [Marshalleck, Francis E.] Indiana Univ Sch Med, Riley Hosp Children, Dept Radiol, Indianapolis, IN USA. [Sidhu, Manrita K.] Univ Washington, Dept Radiol, Seattle Childrens Hosp, Seattle, WA 98195 USA. [Connolly, Bairbre L.; Temple, Michael J.] Univ Toronto, Hosp Sick Children, Ctr Image Guided Therapy, Toronto, ON M5G 1X8, Canada. [Heran, Manraj K. S.] Vancouver Gen Hosp, Dept Radiol, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. [Towbin, Richard B.] Phoenix Childrens Hosp, Dept Radiol, Phoenix, AZ USA. [Saad, Wael A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Cahill, Ann Marie] Childrens Hosp Philadelphia, Dept Intervent Radiol, Philadelphia, PA 19104 USA. [Crowley, John] Univ Pittsburgh, Childrens Hosp Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. [Cardella, John F.] Geisinger Hlth Syst, Dept Radiol, Danville, PA USA. [Hohenwalter, Eric J.] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Dept Radiol, Milwaukee, WI 53226 USA. [Roebuck, Derek J.] Great Ormond St Hosp Sick Children, Dept Radiol, London, England. [Walker, T. Gregory] Massachusetts Gen Hosp, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. RP Hogan, MJ (reprint author), Care Of Debbie Katsarelis, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM mark.hogan@nationwidechildrens.org NR 62 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2012 VL 23 IS 11 BP 1397 EP 1402 DI 10.1016/j.jvir.2012.06.016 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 039SX UT WOS:000311267900001 PM 23101912 ER PT J AU Patel, VI Lancaster, RT Mukhopadhyay, S Aranson, NJ Conrad, MF LaMuraglia, GM Kwolek, CJ Cambria, RP AF Patel, Virendra I. Lancaster, Robert T. Mukhopadhyay, Shankha Aranson, Nathan J. Conrad, Mark F. LaMuraglia, Glenn M. Kwolek, Christopher J. Cambria, Richard P. TI Impact of chronic kidney disease on outcomes after abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 16-18, 2011 CL Providence, RI SP New England Soc Vasc Surg ID GLOMERULAR-FILTRATION-RATE; AFFAIRS SURGICAL RISK; MORTALITY; QUALITY; POPULATION; ADJUSTMENT; CARE; CREATININE; EXPERIENCE; MORBIDITY AB Objective: Chronic kidney disease (CKD) is associated with increased morbidity and death after open abdominal aortic aneurysm (AAA) repair (OAR). This study highlights the effect of CKD on outcomes after endovascular AAA (EVAR) and OAR in contemporary practice. Methods: The National Surgical Quality Improvement Program (NSQIP) Participant Use File (2005-2008) was queried by Current Procedural Terminology (American Medical Association, Chicago, Ill) code to identify EVAR or OAR patients, who were grouped by CKD class as having mild (CKD class 1 or 2), moderate (CKD class 3), or severe (CKD class 4 or 5) renal disease. Propensity score analysis was performed to match OAR and EVAR patients with mild CKD with those with moderate or severe CKD. Comparative analysis of mortality and clinical outcomes was performed based on CKD strata. Results: We identified 8701 patients who were treated with EVAR (n = 5811) or OAR (n = 2890) of intact AAAs. Mild, moderate, and severe CKD was present in 63%, 30%, and 7%, respectively. CKD increased (P < .01) overall mortality, with rates of 1.7% (mild), 5.3% (moderate), and 7.7% (severe) in unmatched patients undergoing EVAR or OAR. Operative mortality rates in patients with severe CKD were as high as 6.2% for EVAR and 10.3% for OAR. Severity of CKD was associated with increasing frequency of risk factors; therefore, propensity matching to control for comorbidities was performed, resulting in similar baseline clinical and demographic features of patients with mild compared with those with moderate or severe disease. In propensity-matched cohorts, moderate CKD increased the risk of 30-day mortality for EVAR (1.9% mild vs 3.2% moderate; P = .013) and OAR (3.1% mild vs 8.4% moderate; P < .0001). Moderate CKD was also associated with increased morbidity in patients treated with EVAR (8.3% mild vs 12.8% moderate; P < .0001) or OAR (25.2% mild vs 32.4% moderate; P = .001). Similarly, severe CKD increased the risk of 30-day mortality for EVAR (2.6% mild vs 5.7% severe; P = .0081) and OAR (4.1% mild vs 9.9% severe; P = .0057). Severe CKD was also associated with increased morbidity in patients treated with EVAR (10.6% mild vs 19.2% severe; P < .0001) or OAR (31.1% mild vs 39.6% severe; P = .04). Conclusions: The presence of moderate or severe CKD in patients considered for AAA repair is associated with significantly increased mortality and therefore should figure prominently in clinical decision making. The high mortality of AAA repair in patients with severe CKD is such that elective repair in such patients is not advised, except in extenuating clinical circumstances. (J Vasc Surg 2012;56:1206-13.) C1 [Patel, Virendra I.; Lancaster, Robert T.; Mukhopadhyay, Shankha; Aranson, Nathan J.; Conrad, Mark F.; LaMuraglia, Glenn M.; Kwolek, Christopher J.; Cambria, Richard P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Patel, VI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, 15 Parkman St,Wang ACC 440, Boston, MA 02114 USA. EM vpatel4@partners.org NR 31 TC 22 Z9 22 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2012 VL 56 IS 5 BP 1206 EP 1213 DI 10.1016/j.jvs.2012.04.037 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 028ND UT WOS:000310428200002 PM 22857808 ER PT J AU Foley, PJ Criado, FJ Farber, MA Kwolek, CJ Mehta, M White, RA Lee, WA Tuchek, JM Fairman, RM AF Foley, Paul J. Criado, Frank J. Farber, Mark A. Kwolek, Christopher J. Mehta, Manish White, Rodney A. Lee, W. Anthony Tuchek, J. Michael Fairman, Ronald M. CA VALOR Investigators TI Results with the Talent thoracic stent graft in the VALOR trial SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Eastern-Vascular-Society CY SEP 22-24, 2011 CL National Harbor, MD SP Eastern Vasc Soc ID AORTIC-ANEURYSM REPAIR; OPEN-SURGICAL REPAIR; ENDOVASCULAR REPAIR; INTERMEDIATE-TERM; ZENITH TX1; EXPERIENCE; MANAGEMENT; OUTCOMES; LESIONS AB Objective: We report the 5-year outcomes of thoracic endovascular aneurysm repair (TEVAR) using the Medtronic Vascular Talent Thoracic Stent Graft System (Medtronic Vascular, Santa Rosa, Calif) in patients considered low or moderate risk for open surgical repair. Methods: The Evaluation of the Medtronic Vascular Talent Thoracic Stent Graft System for the Treatment of Thoracic Aortic Aneurysms (VALOR) trial was a prospective, nonrandomized, multicenter, pivotal study conducted at 38 U. S. sites. Between December 2003 and June 2005, VALOR enrolled 195 patients who were low or moderate risk (0, 1, and 2) per the modified Society for Vascular Surgery and American Association for Vascular Surgery criteria. The patients had fusiform thoracic aortic aneurysms (TAAs) and/or focal saccular TAAs/penetrating atherosclerotic ulcers. Standard follow-up interval examinations were conducted at 1 month, 6 months, 1 year, and annually thereafter. Results: Over the 5-year follow-up, 76 deaths occurred (43.9%). Freedom from all-cause mortality was 83.9% at 1 year and 58.5% at 5 years. Most deaths were due to cardiac, pulmonary or cancer-related causes. Freedom from aneurysm-related mortality (ARM) was 96.9% at 1 year and 96.1% at 5 years. There was only 1 case of ARM after the first year of follow-up. Over the 5-year follow-up period, four patients were converted to open surgery and four patients experienced aneurysm rupture. The 5-year freedom from aneurysm rupture was 97.1% and the 5-year freedom from conversion to surgery was 97.1%. The incidence of stent graft migration (> 10 mm) was <= 1.8% in each year of follow-up. The rate of type I endoleak was 4.6% at 1 month, 6.3% from 1 month to 1 year, and 3.8% during year 5. The rate of type III endoleak was 1.3% at 1 month, 1.9% from 1 month to 1 year, and 1.9% during year 5. Through 5 years, 28 patients (14.4%) underwent 31 additional endovascular procedures on the original target lesion. The 5-year freedom from secondary endovascular procedures was 81.5%. Conclusions: Through 5-year follow-up in patients who were candidates for open surgical repair, TEVAR using the Talent Thoracic Stent Graft System has demonstrated sustained protection from ARM, aneurysm rupture, and conversion to surgery, and durable stent graft performance. Close patient follow-up remains essential after TEVAR. (J Vasc Surg 2012;56:1214-21.) C1 [Foley, Paul J.] Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Criado, Frank J.] Union Mem Hosp, Baltimore, MD USA. [Farber, Mark A.] Univ N Carolina, Chapel Hill, NC USA. [Kwolek, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mehta, Manish] Albany Med Ctr, Albany, NY USA. [White, Rodney A.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Lee, W. Anthony] Christine E Lynn Heart & Vasc Inst, Boca Raton, FL USA. [Tuchek, J. Michael] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. RP Foley, PJ (reprint author), Hosp Univ Penn, Dept Surg, 3400 Spruce St,4 Silverstein Pavil, Philadelphia, PA 19104 USA. EM foleyp@uphs.upenn.edu NR 23 TC 14 Z9 14 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2012 VL 56 IS 5 BP 1214 EP U33 DI 10.1016/j.jvs.2012.04.071 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 028ND UT WOS:000310428200003 PM 22925732 ER PT J AU Shusharina, N Sharp, G AF Shusharina, Nadezhda Sharp, Gregory TI Image registration using radial basis functions with adaptive radius SO MEDICAL PHYSICS LA English DT Article DE image registration; point landmark; manual; radial basis functions; adaptive algorithm ID NONRIGID REGISTRATION; MEDICAL IMAGES; DEFORMATIONS; SPLINES; SUPPORT; HEAD AB Purpose: Deformable registration of medical images often requires initial rigid alignment. Because of variations in the articulation of bony structures, rigid alignment can capture only limited regions of the image. We propose a method that allows us to compensate for misalignment of mobile parts, which leads to improved accuracy of deformable registration. The method is based on matching landmarks using radial basis functions (RBF) with adaptive radius. Methods: Based on the assumption that the compactly positioned landmarks likely delineate an anatomic structure whose position needs to be corrected, the algorithm incorporates unsupervised clustering of landmarks based on their positions within the reference image. It calculates an appropriate RBF radius based on the set of pairwise distances between landmarks within the cluster. The algorithm distinguishes between clusters of different size and between clusters of spherical and elongated shape, and assigns the optimal RBF radius for each cluster in order to restrict the deformation field to the closest vicinity of the structure of interest. Results: Experiments with synthetic images demonstrate sensitivity of registration results to the choice of the radius of RBF support. We have statistically validated the methods on a large set of pulmonary landmarks. We also tested the method on medical use cases that show that it is potentially advantageous for initial registration of images with large spatial dislocations. Conclusions: The results of registration of CT images demonstrate that an automated selection of the RBF radius simplifies the registration routine and improves the registration quality. The selection is based on two criteria of preserving diffeomorphism of deformation and localization of the deformation within a desired area of the image. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4756932] C1 [Shusharina, Nadezhda; Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Shusharina, N (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM nshusharina@partners.org FU Ira J. Spiro translational research award; National Institutes of Health (NIH) [NCI 6-PO1CA21239]; MGH on NIH NCI [C06CA059267]; National Institutes of Health through the NIH Roadmap for Medical Research [2-U54EB005149-06] FX Funding for this work was provided by an Ira J. Spiro translational research award, by the National Institutes of Health (NIH) NCI 6-PO1CA21239, and by the Federal share of program income earned by MGH on NIH NCI-C06CA059267. This work is part of the National Alliance for Medical Image Computing (NA-MIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant No. 2-U54EB005149-06. NR 19 TC 2 Z9 2 U1 3 U2 6 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2012 VL 39 IS 11 BP 6542 EP 6549 DI 10.1118/1.4756932 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 032NP UT WOS:000310726300003 PM 23127049 ER PT J AU Alpert, N Fang, YHD El Fakhri, G AF Alpert, Nathaniel Fang, Yu-Hua Dean El Fakhri, Georges TI Single-scan rest/stress imaging F-18-labeled flow tracers SO MEDICAL PHYSICS LA English DT Article DE kinetic modeling; rest/stress; cardiac PET; myocardial blood flow ID POSITRON-EMISSION-TOMOGRAPHY; SPLIT-DOSE I-123-IODOAMPHETAMINE; MYOCARDIAL BLOOD-FLOW; PARAMETRIC IMAGES; EXERCISE STRESS; PET; PERFUSION; ADENOSINE; AGENT; SPECT AB Purpose: The authors report a novel measurement strategy to obtain both rest and stress blood flow during a single, relatively short, scan session. Methods: Measurement of rest-stress myocardial blood flow with long-lived tracers usually requires separate scan sessions to remove the confounding effects of residual radioactivity concentration in the blood and tissue. The innovation of this method is to treat the rest-stress scan as a single entity in which the flow parameters change due to pharmacological challenge. With this approach the fate of a tracer molecule is naturally accounted for, no matter if it was introduced during the rest or stress phase of the study. Two new dual-injection kinetic models are considered that represent the response to pharmacological stress as a transitional or transient increase of myocardial blood flow. The authors present the theory of the method followed by the specific application of the theory to F-18-Flurpiridaz, a new myocardial flow-imaging agent. Results: Myocardial blood flow was accurately and precisely estimated from a single-scan rest/stress study for the long half-lived tracer 18F-Flurpiridaz. By accounting for the time-dependence of the kinetic parameters, the proposed models achieved good accuracy and precision (5%) under different vasodilators and different ischemic states. Conclusions: Detailed simulations predict that accurate and precise rest-stress blood flow measurements can be obtained in 20-30 min. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4754585] C1 [El Fakhri, Georges] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Ctr Adv Radiol Sci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Ctr Adv Radiol Sci, 55 Fruit St, Boston, MA 02114 USA. EM elfakhri@pet.mgh.harvard.edu FU National Institutes of Health (NIH) [R56-HL095076, R01-HL110241] FX This work was supported by National Institutes of Health (NIH) Grant Nos. R56-HL095076 and R01-HL110241. Nathaniel Alpert and Yu-Hua Dean Fang contributed equally to this work. The authors express their gratitude to Lantheus Medical Imaging for providing them with the clinical data used for designing the kinetic model. The authors report no conflicts of interests in conducting the research. NR 34 TC 4 Z9 4 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2012 VL 39 IS 11 BP 6609 EP 6620 DI 10.1118/1.4754585 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 032NP UT WOS:000310726300009 PM 23127055 ER PT J AU Perl, J Shin, J Schumann, J Faddegon, B Paganetti, H AF Perl, J. Shin, J. Schuemann, J. Faddegon, B. Paganetti, H. TI TOPAS: An innovative proton Monte Carlo platform for research and clinical applications SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; simulation; proton therapy; treatment head ID DOSE CALCULATION; GEANT4 SIMULATION; NUCLEAR-MODELS; PROMPT GAMMA; THERAPY; BEAM; RADIOTHERAPY; FIELDS; RANGE; UNCERTAINTIES AB Purpose: While Monte Carlo particle transport has proven useful in many areas (treatment head design, dose calculation, shielding design, and imaging studies) and has been particularly important for proton therapy (due to the conformal dose distributions and a finite beam range in the patient), the available general purpose Monte Carlo codes in proton therapy have been overly complex for most clinical medical physicists. The learning process has large costs not only in time but also in reliability. To address this issue, we developed an innovative proton Monte Carlo platform and tested the tool in a variety of proton therapy applications. Methods: Our approach was to take one of the already-established general purpose Monte Carlo codes and wrap and extend it to create a specialized user-friendly tool for proton therapy. The resulting tool, TOol for PArticle Simulation (TOPAS), should make Monte Carlo simulation more readily available for research and clinical physicists. TOPAS can model a passive scattering or scanning beam treatment head, model a patient geometry based on computed tomography (CT) images, score dose, fluence, etc., save and restart a phase space, provides advanced graphics, and is fully four-dimensional (4D) to handle variations in beam delivery and patient geometry during treatment. A custom-designed TOPAS parameter control system was placed at the heart of the code to meet requirements for ease of use, reliability, and repeatability without sacrificing flexibility. Results: We built and tested the TOPAS code. We have shown that the TOPAS parameter system provides easy yet flexible control over all key simulation areas such as geometry setup, particle source setup, scoring setup, etc. Through design consistency, we have insured that user experience gained in configuring one component, scorer or filter applies equally well to configuring any other component, scorer or filter. We have incorporated key lessons from safety management, proactively removing possible sources of user error such as line-ordering mistakes. We have modeled proton therapy treatment examples including the UCSF eye treatment head, the MGH stereotactic alignment in radiosurgery treatment head and the MGH gantry treatment heads in passive scattering and scanning modes, and we have demonstrated dose calculation based on patient-specific CT data. Initial validation results show agreement with measured data and demonstrate the capabilities of TOPAS in simulating beam delivery in 3D and 4D. Conclusions: We have demonstrated TOPAS accuracy and usability in a variety of proton therapy setups. As we are preparing to make this tool freely available for researchers in medical physics, we anticipate widespread use of this tool in the growing proton therapy community. (c) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4758060] C1 [Perl, J.] SLAC Natl Accelerator Lab, Menlo Pk, CA 94025 USA. [Shin, J.; Faddegon, B.] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. [Schuemann, J.; Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Schuemann, J.; Paganetti, H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Perl, J (reprint author), SLAC Natl Accelerator Lab, 2575 Sand Hill Rd, Menlo Pk, CA 94025 USA. EM perl@slac.stanford.edu FU National Institutes of Health/National Cancer Institute (NIH/NCI) [R01 CA 140735-01] FX This work was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) under R01 CA 140735-01. The authors would like to thank Makoto Asai (SLAC) for many useful discussions of how best to exploit the fundamental architecture of Geant4 and Daren Sawkey (UCSF) for providing the early version of our phase space IO module. The authors appreciate the information provided by Inder Daftari (UCSF) and Tsukasa Aso (Toyama National College) on the Crocker Lab beam line. They would also like to thank Stephen Dowdell (MGH) for an early version of the scanning quadrupole model of the MGH scanning beamline and Ben Clasie (MGH) for discussions regarding the MGH scanning system. Jule Daartz (MGH) provided an early Geant4 model of the STAR treatment head. The authors thank Forrest Iandola (SLAC) for feedback on the parameter system design and Mauro Testa (MGH), who provided theMGH SOBP and profile measurements. The authors thank their Alpha testers at MGH, specifically Marta Bueno, Clemens Grassberger, and Joost Verburg. NR 53 TC 90 Z9 90 U1 5 U2 30 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2012 VL 39 IS 11 BP 6818 EP 6837 DI 10.1118/1.4758060 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 032NP UT WOS:000310726300030 PM 23127075 ER PT J AU Pursley, J Risholm, P Fedorov, A Tuncali, K Fennessy, FM Wells, WM Tempany, CM Cormack, RA AF Pursley, Jennifer Risholm, Petter Fedorov, Andriy Tuncali, Kemal Fennessy, Fiona M. Wells, William M., III Tempany, Clare M. Cormack, Robert A. TI A Bayesian nonrigid registration method to enhance intraoperative target definition in image-guided prostate procedures through uncertainty characterization SO MEDICAL PHYSICS LA English DT Article DE deformable probabilistic registration; prostate; brachytherapy ID DEFORMABLE REGISTRATION; RADIATION-THERAPY; RADICAL PROSTATECTOMY; CANCER; BRACHYTHERAPY; VALIDATION; ALGORITHM; ACCURACY AB Purpose: This study introduces a probabilistic nonrigid registration method for use in image-guided prostate brachytherapy. Intraoperative imaging for prostate procedures, usually transrectal ultrasound (TRUS), is typically inferior to diagnostic-quality imaging of the pelvis such as endorectal magnetic resonance imaging (MRI). MR images contain superior detail of the prostate boundaries and provide substructure features not otherwise visible. Previous efforts to register diagnostic prostate images with the intraoperative coordinate system have been deterministic and did not offer a measure of the registration uncertainty. The authors developed a Bayesian registration method to estimate the posterior distribution on deformations and provide a case-specific measure of the associated registration uncertainty. Methods: The authors adapted a biomechanical-based probabilistic nonrigid method to register diagnostic to intraoperative images by aligning a physician's segmentations of the prostate in the two images. The posterior distribution was characterized with a Markov Chain Monte Carlo method; the maximum a posteriori deformation and the associated uncertainty were estimated from the collection of deformation samples drawn from the posterior distribution. The authors validated the registration method using a dataset created from ten patients with MRI-guided prostate biopsies who had both diagnostic and intraprocedural 3 Tesla MRI scans. The accuracy and precision of the estimated posterior distribution on deformations were evaluated from two predictive distance distributions: between the deformed central zone-peripheral zone (CZ-PZ) interface and the physician-labeled interface, and based on physician-defined landmarks. Geometric margins on the registration of the prostate's peripheral zone were determined from the posterior predictive distance to the CZ-PZ interface separately for the base, mid-gland, and apical regions of the prostate. Results: The authors observed variation in the shape and volume of the segmented prostate in diagnostic and intraprocedural images. The probabilistic method allowed us to convey registration results in terms of posterior distributions, with the dispersion providing a patient-specific estimate of the registration uncertainty. The median of the predictive distance distribution between the deformed prostate boundary and the segmented boundary was <= 3 mm (95th percentiles within +/- 4 mm) for all ten patients. The accuracy and precision of the internal deformation was evaluated by comparing the posterior predictive distance distribution for the CZ-PZ interface for each patient, with the median distance ranging from -0.6 to 2.4 mm. Posterior predictive distances between naturally occurring landmarks showed registration errors of <= 5 mm in any direction. The uncertainty was not a global measure, but instead was local and varied throughout the registration region. Registration uncertainties were largest in the apical region of the prostate. Conclusions: Using a Bayesian nonrigid registration method, the authors determined the posterior distribution on deformations between diagnostic and intraprocedural MR images and quantified the uncertainty in the registration results. The feasibility of this approach was tested and results were positive. The probabilistic framework allows us to evaluate both patient-specific and location-specific estimates of the uncertainty in the registration result. Although the framework was tested on MR-guided procedures, the preliminary results suggest that it may be applied to TRUS-guided procedures as well, where the addition of diagnostic MR information may have a larger impact on target definition and clinical guidance. (C) 2012 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4760992] C1 [Pursley, Jennifer; Cormack, Robert A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, Boston, MA 02115 USA. [Risholm, Petter; Fedorov, Andriy; Tuncali, Kemal; Fennessy, Fiona M.; Wells, William M., III; Tempany, Clare M.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Sch Med, Boston, MA 02115 USA. RP Pursley, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA. EM jpursley@partners.org OI Cormack, Robert/0000-0001-5553-9984; Fedorov, Andrey/0000-0003-4806-9413 FU National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health [P41EB015898, P41RR019703, 1R01CA111288-01A1, P01-CA67165, U01CA151261] FX This project was supported by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health through Grant Nos. P41EB015898, P41RR019703, 1R01CA111288-01A1, P01-CA67165, and U01CA151261. The authors thank Barbara Silver, Clinical Research Coordinator, Dana-Farber Cancer Institute, Harvard Medical School, for editing the paper. NR 30 TC 5 Z9 5 U1 0 U2 11 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2012 VL 39 IS 11 BP 6858 EP 6867 DI 10.1118/1.4760992 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 032NP UT WOS:000310726300033 PM 23127078 ER PT J AU Mushti, C Papisov, MI AF Mushti, Chandra Papisov, Mikhail I. TI Radioiodination of Aryl-Alkyl Cyclic Sulfates SO MOLECULES LA English DT Article DE iodine; cyclic sulfate; Positron Emission Tomography; I-124; enzyme substrate ID ARYLSULFATASE AB Among the currently available positron emitters suitable for Positron Emission Tomography (PET), I-124 has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes I-124 very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel I-124 labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [I-124] iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester. C1 [Mushti, Chandra; Papisov, Mikhail I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mushti, Chandra; Papisov, Mikhail I.] Shriners Hosp Children, Boston, MA 02114 USA. RP Mushti, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Room 439,51 Blossom St, Boston, MA 02114 USA. EM cmushti@partners.org; papisov@helix.mgh.harvard.edu OI Papisov, Mikhail/0000-0003-4716-2122 FU Shriners Hospitals for Children [85310]; Shire HGT FX This research was supported by Grant 85310 from Shriners Hospitals for Children and a grant from Shire HGT. Authors thank M. Gagne for logistical support and E. Papisov for assistance with editing. NR 15 TC 1 Z9 1 U1 0 U2 8 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD NOV PY 2012 VL 17 IS 11 BP 13266 EP 13274 DI 10.3390/molecules171113266 PG 9 WC Chemistry, Organic SC Chemistry GA 041VD UT WOS:000311428400060 PM 23135631 ER PT J AU Epa, VC Burden, FR Tassa, C Weissleder, R Shaw, S Winkler, DA AF Epa, V. Chandana Burden, Frank R. Tassa, Carlos Weissleder, Ralph Shaw, Stanley Winkler, David A. TI Modeling Biological Activities of Nanoparticles SO NANO LETTERS LA English DT Article DE Nanoparticle toxicity; model prediction; apoptosis; cellular uptake; Bayesian methods ID REGULARIZED NEURAL-NETWORKS; BOVINE SERUM-ALBUMIN; ROBUST QSAR MODELS; DESCRIPTOR SELECTION; PARTICLES; ADSORPTION AB Products are increasingly incorporating nanomaterials, but we have a poor understanding of their adverse effects. To assess risk, regulatory authorities need more experimental testing of nanoparticles. Computational models play a complementary role in allowing rapid prediction of potential toxicities of new and modified nanomaterials. We generated quantitative, predictive models of cellular uptake and apoptosis induced by nanoparticles for several cell types. We illustrate the potential of computational methods to make a contribution to nanosafety. C1 [Burden, Frank R.; Winkler, David A.] CSIRO Mat Sci & Engn, Clayton, Vic 3168, Australia. [Epa, V. Chandana] CSIRO Mat Sci & Engn, Parkville, Vic 3052, Australia. [Winkler, David A.] Monash Inst Pharmaceut Sci, Parkville, Vic 30152, Australia. [Tassa, Carlos; Weissleder, Ralph; Shaw, Stanley] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Tassa, Carlos; Weissleder, Ralph; Shaw, Stanley] Harvard Univ, Sch Med, Boston, MA USA. [Shaw, Stanley] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Winkler, DA (reprint author), CSIRO Mat Sci & Engn, Bayview Ave, Clayton, Vic 3168, Australia. EM dave.winkler@csiro.au RI Winkler, David/A-3774-2008; OI Winkler, David/0000-0002-7301-6076; Winkler, David Alan/0000-0003-2423-674X FU CSIRO Advanced Materials Transformational Capability Platform FX The authors acknowledge support of the CSIRO Advanced Materials Transformational Capability Platform and assistance from Dr. Richard Evans on chemical reaction products. S.S., CT., and R.W. generated the experimental data; V.E., F.B., and D.W. selected optimal structural descriptors, developed and validated the QSAR models, and discussed the results. V.E. and D.W. wrote the paper. NR 22 TC 61 Z9 63 U1 3 U2 85 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD NOV PY 2012 VL 12 IS 11 BP 5808 EP 5812 DI 10.1021/nl303144k PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 039KJ UT WOS:000311244400062 PM 23039907 ER PT J AU De, S Michor, F AF De, Subhajyoti Michor, Franziska TI Analyzing the association of SCNA boundaries with replication timing Response SO NATURE BIOTECHNOLOGY LA English DT Letter ID COPY-NUMBER; GENOME C1 [De, Subhajyoti; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [De, Subhajyoti; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP De, S (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2012 VL 30 IS 11 BP 1045 EP 1046 DI 10.1038/nbt.2414 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 037FL UT WOS:000311087500018 ER PT J AU Martell, JD Deerinck, TJ Sancak, Y Poulos, TL Mootha, VK Sosinsky, GE Ellisman, MH Ting, AY AF Martell, Jeffrey D. Deerinck, Thomas J. Sancak, Yasemin Poulos, Thomas L. Mootha, Vamsi K. Sosinsky, Gina E. Ellisman, Mark H. Ting, Alice Y. TI Engineered ascorbate peroxidase as a genetically encoded reporter for electron microscopy SO NATURE BIOTECHNOLOGY LA English DT Article ID MITOCHONDRIAL CALCIUM UNIPORTER; HORSERADISH-PEROXIDASE; HIGH-RESOLUTION; CRYSTAL-STRUCTURE; ACID COMPLEX; PROTEIN; CELLS; LIGHT; LOCALIZATION; FLUORESCENCE AB Electron microscopy (EM) is the standard method for imaging cellular structures with nanometer resolution, but existing genetic tags are inactive in most cellular compartments(1) or require light and can be difficult to use(2). Here we report the development of 'APEX', a genetically encodable EM tag that is active in all cellular compartments and does not require light. APEX is a monomeric 28-kDa peroxidase that withstands strong EM fixation to give excellent ultrastructural preservation. We demonstrate the utility of APEX for high-resolution EM imaging of a variety of mammalian organelles and specific proteins using a simple and robust labeling procedure. We also fused APEX to the N or C terminus of the mitochondrial calcium uniporter (MCU), a recently identified channel whose topology is disputed(3,4). These fusions give EM contrast exclusively in the mitochondrial matrix, suggesting that both the N and C termini of MCU face the matrix. Because APEX staining is not dependent on light activation, APEX should make EM imaging of any cellular protein straightforward, regardless of the size or thickness of the specimen. C1 [Martell, Jeffrey D.; Ting, Alice Y.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Deerinck, Thomas J.; Sosinsky, Gina E.; Ellisman, Mark H.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, Ctr Res Biol Syst, La Jolla, CA 92093 USA. [Sancak, Yasemin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Sancak, Yasemin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sancak, Yasemin; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sancak, Yasemin; Mootha, Vamsi K.] Broad Inst, Cambridge, MA USA. [Poulos, Thomas L.] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92717 USA. [Poulos, Thomas L.] Univ Calif Irvine, Dept Chem, Irvine, CA 92717 USA. [Poulos, Thomas L.] Univ Calif Irvine, Dept Pharmaceut Sci, Irvine, CA USA. [Sosinsky, Gina E.; Ellisman, Mark H.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Ting, AY (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA. EM ating@mit.edu FU US National Institutes of Health [DP1 OD003961, P41RR004050, P41GM103412, GM065937, GM072881, GM077465, GM42614]; National Science Foundation Graduate Research Fellowship; National Defense Science and Engineering Graduate Fellowship FX We thank A. Keating for use of her gel filtration chromatography system and A. Thor, A. Cone and M. Terada for assistance with electron tomography. The IMS-APEX EM data were obtained by H.-W. Rhee, P. Zou, J.D.M. and E. Vasile (Microscopy and Imaging Core Facility, Koch Institute at MIT). C. Uttamapinant (MIT) and H. Fraser (Stanford) provided helpful feedback on the manuscript. Funding was provided by US National Institutes of Health grants DP1 OD003961 (A.Y.T.), P41RR004050 (M.H.E.), P41GM103412 (M.H.E.), GM065937 (G. E. S.), GM072881 (G.E.S.), GM077465 (V.K.M.) and GM42614 (T.L.P.). J.D.M. was supported by a National Science Foundation Graduate Research Fellowship and a National Defense Science and Engineering Graduate Fellowship. NR 38 TC 134 Z9 137 U1 6 U2 65 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2012 VL 30 IS 11 BP 1143 EP + DI 10.1038/nbt.2375 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 037FL UT WOS:000311087500035 PM 23086203 ER PT J AU Larauche, M Mulak, A Kim, YS Labus, J Million, M Tache, Y AF Larauche, M. Mulak, A. Kim, Y. S. Labus, J. Million, M. Tache, Y. TI Visceral analgesia induced by acute and repeated water avoidance stress in rats: sex difference in opioid involvement SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE colorectal distension; defecation; estrous cycle; manometry; naloxone; sex difference; stress-related visceral analgesia; water avoidance stress ID IRRITABLE-BOWEL-SYNDROME; CORTICOTROPIN-RELEASING-FACTOR; GENDER-DIFFERENCES; INDUCED ANTINOCICEPTION; INDIVIDUAL-DIFFERENCES; COLORECTAL DISTENSION; PSYCHOLOGICAL STRESS; DISTINCT MECHANISMS; GONADAL-HORMONES; COLONIC FUNCTION AB Background Chronic psychological stress-induced alterations in visceral sensitivity have been predominantly assessed in male rodents. We investigated the effect of acute and repeated water avoidance stress (WAS) on the visceromotor response (VMR) to colorectal distension (CRD) and the role of opioids in male and cycling female Wistar rats using a novel non-invasive manometric technique. Methods After a baseline VMR (1st CRD, day 0), rats were exposed to WAS (1 h day-1) either once or for four consecutive days, without injection or with naloxone (1 mg kg-1) or saline injected subcutaneously before each WAS session. Key Results The VMR to CRD recorded on day 1 or 4 immediately after the last WAS was reduced in both females and males. The visceral analgesia was mainly naloxone-dependent in females, but naloxone-independent in males. In non-injected animals, on days 2 and 5, VMR was not significantly different from baseline in males whereas females exhibited a significant VMR increase at 60 mmHg on day 5. Basal CRD and CRD on days 1, 2, and 5 in both sexes without WAS induced similar VMR. Conclusions & Inferences When monitored non-invasively, psychological stress induces an immediate poststress visceral analgesia mediated by an opiate signaling system in females while naloxone-independent in males, and hyperalgesia at 24 h after repeated stress only in females. These data highlight the importance of sex-specific interventions to modulate visceral pain response to stress. C1 [Larauche, M.] VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Digest Dis Res Ctr Anim Core, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Oppenheimer Family Ctr Neurobiol Stress, Div Digest Dis, Los Angeles, CA 90024 USA. RP Larauche, M (reprint author), VA Greater Los Angeles Healthcare Syst, Ctr Neurobiol Stress, CURE Digest Dis Res Ctr Anim Core, 11301 Wilshire Blvd,CURE Bldg 115,Room 111, Los Angeles, CA 90073 USA. EM mlarauche@mednet.ucla.edu OI Larauche, Muriel/0000-0003-3320-3675 FU National Institutes of Health [P50 DK-64539, DK -41301, R01 DK-33061]; Kosciuszko Foundation; Soongsan Fellowship in Wonkwang University; Career Scientist Award [K01 DK088937, K08 DK071626, R03 DK084169]; [DK 78676] FX This work was supported by National Institutes of Health grants P50 DK-64539 and Center Grant DK -41301 (Animal Core), R01 DK-33061, and VA Career Scientist Award (YT), K01 DK088937 (ML), K08 DK071626 (JL), R03 DK084169 (JL), The Kosciuszko Foundation (AM), The Soongsan Fellowship in Wonkwang University 2009 (YSK), and DK 78676 (MM). NR 62 TC 17 Z9 17 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD NOV PY 2012 VL 24 IS 11 DI 10.1111/j.1365-2982.2012.01980.x PG 12 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 019OG UT WOS:000309748600010 PM 22776034 ER PT J AU Ewald, CY Li, C AF Ewald, Collin Y. Li, Chris TI The secreted Alzheimer-related amyloid precursor protein fragment has an essential role in C. elegans SO PRION LA English DT Article DE Alzheimer disease; APL-1; C. elegans; insulin; receptor protein tyrosine phosphatase ID CAENORHABDITIS-ELEGANS; FAMILY-MEMBERS; DISEASE; APL-1; GENE; MICE; LONGEVITY; MUTATION; RECEPTOR; INSULIN AB Mutations in the gene encoding the amyloid precursor protein (APP) or the enzymes that process APP are correlated with familial Alzheimer disease. Alzheimer disease is also associated with insulin resistance (type 2 diabetes). In our recently published study, 1 we obtained genetic evidence that the extracellular fragment of APL-1, the C. elegans ortholog of human APP, may act as a signaling molecule to modulate insulin and nuclear hormone pathways in C. elegans development. In addition, independent of insulin and nuclear hormone signaling, high levels of the extracellular fragment of APL-1 (sAPL-1) leads to a temperature-sensitive embryonic lethality, which is dependent on activity of a predicted receptor protein tyrosine phosphatase (MOA-1/R155.2). Furthermore, this embryonic lethality is enhanced by knockdown of a predicted prion-like protein (pqn-29). The precise molecular mechanisms underlying these processes remain to be determined. Here, we present hypothetical models as to how sAPL-1 signaling influences metabolic and developmental pathways. Together, with previous findings in mammals that the extracellular domain of mammalian APP (sAPP) binds to a death-receptor,(2) our findings support the model that sAPP signaling affects critical biological processes. C1 [Li, Chris] CUNY, Grad Ctr, New York, NY USA. [Ewald, Collin Y.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Ewald, Collin Y.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Li, Chris] CUNY, Dept Biol, New York, NY 10021 USA. RP Li, C (reprint author), CUNY, Grad Ctr, New York, NY USA. EM cli@sci.ccny.cuny.edu RI Ewald, Collin/K-6303-2015 OI Ewald, Collin/0000-0003-1166-4171 FU National Institutes of Health; National Science Foundation; Swiss National Science Foundation FX This work was supported by grants from the National Institutes of Health and National Science Foundation (C. L.) and from the Swiss National Science Foundation (C.Y.E.). NR 26 TC 1 Z9 2 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD NOV-DEC PY 2012 VL 6 IS 5 DI 10.4161/pri.22310 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 040RR UT WOS:000311341100005 PM 23044509 ER PT J AU Duan, M Lee, J Bittner, EA AF Duan, Melissa Lee, Jarone Bittner, Edward A. TI Dexmedetomidine for Sedation in the Parturient With Respiratory Failure Requiring Noninvasive Ventilation SO RESPIRATORY CARE LA English DT Article DE respiratory distress; noninvasive ventilation; NIV; pregnancy; dexmedetomidine AB Dexmedetomidine is a selective alpha-2 receptor agonist that possesses both sedative and analgesic properties, with minimal respiratory depression. We report the successful administration of dexmedetomidine on a 16-year-old primigravida woman that allowed the patient to tolerate application of bi-level positive airway pressure ventilation in treatment of acute hypoxemic respiratory failure. C1 [Duan, Melissa; Lee, Jarone; Bittner, Edward A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Surg ICU, Boston, MA 02114 USA. RP Bittner, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med,Surg ICU, 55 Fruit St, Boston, MA 02114 USA. EM ebittner@partners.org OI Lee, Jarone/0000-0002-4532-8523 NR 14 TC 4 Z9 4 U1 0 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD NOV PY 2012 VL 57 IS 11 BP 1967 EP 1969 DI 10.4187/respcare.01733 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 043CU UT WOS:000311521300020 PM 22709960 ER PT J AU Bamne, M Wood, J Chowdari, K Watson, AM Celik, C Mansour, H Klei, L Gur, RC Bradford, LD Calkins, ME Santos, AB Edwards, N Kwentus, J McEvoy, JP Allen, TB Savage, RM Nasrallah, HA Gur, RE Perry, RT Go, RCP Devlin, B Yolken, R Nimgaonkar, VL AF Bamne, Mikhil Wood, Joel Chowdari, Kodavali Watson, Annie M. Celik, Cemil Mansour, Hader Klei, Lambertus Gur, Ruben C. Bradford, L. DiAnne Calkins, Monica E. Santos, Alberto B. Edwards, Neil Kwentus, Joseph McEvoy, Joseph P. Allen, Trina B. Savage, Robert M. Nasrallah, Henry A. Gur, Raquel E. Perry, Rodney T. Go, Rodney C. P. Devlin, Bernie Yolken, Robert Nimgaonkar, Vishwajit L. TI Evaluation of HLA Polymorphisms in Relation to Schizophrenia Risk and Infectious Exposure SO SCHIZOPHRENIA BULLETIN LA English DT Article DE HLA; gene; HSV-1; cytomegalovirus; schizophrenia; African American ID AFRICAN-AMERICANS; COMMON VARIANTS; CONFERRING RISK; EXPLORE RISKS; ASSOCIATION; ANTIBODIES; CYTOMEGALOVIRUS; IMPAIRMENT; PAARTNERS; ANCESTRY AB Background: Genome-wide association studies (C WAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. Method: GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (ISV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. Results: Five SNPs were nominally associated with SZ, adjusted for population admixture (P<.05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. Conclusions: We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples. C1 [Bamne, Mikhil; Wood, Joel; Chowdari, Kodavali; Watson, Annie M.; Celik, Cemil; Mansour, Hader; Devlin, Bernie; Nimgaonkar, Vishwajit L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Devlin, Bernie; Nimgaonkar, Vishwajit L.] Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15213 USA. [Celik, Cemil] GATA Sch Med, Dept Psychiat, Etlik, Turkey. [Klei, Lambertus] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Computat Genet Program, Pittsburgh, PA 15213 USA. [Gur, Ruben C.; Calkins, Monica E.] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Gur, Ruben C.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Bradford, L. DiAnne] Morehouse Sch Med, Dept Psychiat, Atlanta, GA 30310 USA. [Santos, Alberto B.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Edwards, Neil] Univ Tennessee, Dept Psychiat, Coll Med, Memphis, TN USA. [Kwentus, Joseph] Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. [McEvoy, Joseph P.; Allen, Trina B.] Duke Univ, Med Ctr, John Umstead Hosp, Butler, NC USA. [Savage, Robert M.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Nasrallah, Henry A.] Univ Cincinnati, Coll Med, Dept Psychiat & Neurosci, Cincinnati, OH USA. [Gur, Raquel E.] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Philadelphia, PA 19104 USA. [Go, Rodney C. P.] Univ Alabama Birmingham, Dept Epidemiol & Int Hlth, Birmingham, AL USA. [Yolken, Robert] Johns Hopkins Univ, Med Ctr, Stanley Div Dev Neurovirol, Baltimore, MD 21218 USA. RP Nimgaonkar, VL (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM nimga@pitt.edu FU National Institute of Mental Health at the National Institute of Health [MH66006, R01 MH66278, R01 MH066049, R01 MH66181-03, R01 MH66121, R01 MH066005, R01 MH66050, R01 MH66263, R01 MH66004, K08 MH79364]; Stanley Medical Research Institute [07-R1721]; University of Mississippi; Eli Lilly; Astra Zeneca; Pfizer; Bristol Meyers; Johnson Johnson; Takeda; University of Pennsylvania; AstraZeneca; Forest; Lilly; Roche/Genentech; Otsuka; Shire FX National Institute of Mental Health at the National Institute of Health (R01 grant numbers: MH66006 [LDB], R01 MH66278 [BD], R01 MH066049 [NE], R01 MH66181-03 [RCPG], R01 MH66121 [REG], R01 MH066005 [JK], R01 MH66050 [JPM], R01 MH66263 [VLN] and R01 MH66004 [AS], and K08 MH79364 [MC]; The Stanley Medical Research Institute (07-R1721[VLN]).; The authors thank the study participants and research faculty and staff for their time and effort, and they thank the Western Mental Health Center and Dr Thomas Hobbs for their support and contribution to recruitment in Ensley and Birmingham, AL. The following research faculty and staff contributed at the 8 sites: University of Alabama at Birmingham (central administrative site)-Roberta May; Charlie Swanson, Jr, MD; Laura Montgomery-Barefield, MD; Tolulope Aduroja, MD; Ryan Coleman; Rakesha Garner; Lee Prichett, RN; Thomas Kelley, RN; Marguerite Ryan Dickson, PhD; Muktar Aliyu, MD, DrPH; Adrienne Lahti, MD; Duke-Linda Blalock, RN; University of Mississippi-Karen Richardson, MS; Morehouse School of Medicine-Deirdre Evans-Cosby, MD; George W. Woods, MD; Kendaly Meadows, RN; Sandra Cummings, MSW; Cara Stephens, LCSW; and Kent Baker; Medical University of South Carolina-Shirley Hendrix, Cynthia Gilliard, Wanda Smalls-Smith, and Steven McLeod-Bryant; University of Pennsylvania-Felipe Da Silva; Alexandra Duncan-Ramos, MS; Jarrod Gutman; CarlaAnn Henry; Paul Hughett, PhD; Farzin Irani, PhD; Jennifer Jackson Greene, MS; Stephen J. Kanes, MD, PhD; Christian Kohler, MD; David Rice; Devon Seward; Steven Siegel, MD, PhD; Bruce Turetsky, MD; and Robert Witalec; University of Pittsburgh-Mary Miller, LPN; and Frank Fleischer, MBA; University of Tennessee-Kristin Beizai, MD; Marie Tobin, ME); Alyssa English, MD; Richard Sanders, BS; Shelia A. Dempsey, ADN; Martha Velez, CPS; Marianne Smith, BS, MA; Martha Garriott, MS, NCC; Nancy Fowler; Derrick W. Allen, MSSW; Phyllis Meyer, BS, PA; and Lynn Heustess, BS. Drs Allen, Bradford, Calkins, Devlin, Edwards, Go, McEvoy, Nimgaonkar, Santos, Weiner, Wood report no competing interests. Dr Kwentus receives grant support through collaborations of the University of Mississippi with Eli Lilly, Astra Zeneca, Pfizer, Bristol Meyers, Johnson & Johnson, and Takeda. Dr Raquel Gur receives grant support through collaborations of the University of Pennsylvania with AstraZeneca and Pfizer. Dr Henry Nasrallah has received research grants from Forest, Lilly, Roche/Genentech, Otsuka, Shire and honoraria for consulting or speaking at Genentech, Grunenthal, Janssen, Lundbeck, Merck, Novartis, Sunovion, and Boehringer-Inglheim. The other authors did not report any competing interests. NR 29 TC 10 Z9 10 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2012 VL 38 IS 6 BP 1149 EP 1154 DI 10.1093/schbul/sbs087 PG 6 WC Psychiatry SC Psychiatry GA 035KD UT WOS:000310944500010 PM 22966150 ER PT J AU Perez, VB Ford, JM Roach, BJ Loewy, RL Stuart, BK Vinogradov, S Mathalon, DH AF Perez, Veronica B. Ford, Judith M. Roach, Brian J. Loewy, Rachel L. Stuart, Barbara K. Vinogradov, Sophia Mathalon, Daniel H. TI Auditory Cortex Responsiveness During Talking and Listening: Early Illness Schizophrenia and Patients at Clinical High-Risk for Psychosis SO SCHIZOPHRENIA BULLETIN LA English DT Article DE psychosis; clinical high-risk; self-monitoring; forward model; corollary discharge ID COROLLARY DISCHARGE DYSFUNCTION; CORTICAL RESPONSIVENESS; INITIAL PRODROME; HALLUCINATIONS; SPEECH; PERCEPTION; PREDICTION; DISORDERS; RESPONSES; VALIDITY AB Objective: The corollary discharge mechanism is theorized to dampen sensations resulting from our own actions and distinguish them from environmental events. Deficits in this mechanism in schizophrenia may contribute to misperceptions of self-generated sensations as originating from external stimuli. We previously found attenuated speech-related suppression of auditory cortex in chronic patients, consistent with such deficits. Whether this abnormality precedes psychosis onset, emerges early in the illness, and/or progressively worsens with illness chronicity, is unknown. Methods: Event-related potentials (ERPs) were recorded from schizophrenia patients (SZ; n = 75) and age-matched healthy controls (HC; n = 77). A subsample of early illness schizophrenia patients (ESZ; n = 39) was compared with patients at clinical high-risk for psychosis (CHR; n = 35) and to a subgroup of age-matched HC (n = 36) during a Talk-Listen paradigm. The N1 ERP component was elicited by vocalizations as subjects talked (Talk) and heard them played back (Listen). Results: As shown previously, SZ showed attenuated speech-related N1 suppression relative to HC. This was also observed in ESZ. N1 suppression values in CHR were intermediate to HC and ESZ and not statistically distinguishable from either comparison group. Age-corrected N1 Talk-Listen difference Z scores were not correlated with illness duration in the full SZ sample. Conclusions: Putative dysfunction of the corollary discharge mechanism during speech is evident early in the illness and is stable over its course. The intermediate effects in CHR patients may reflect the heterogeneity of this group, requiring longitudinal follow-up data to address if speech-related N1 suppression abnormalities are a risk marker for conversion to psychosis. C1 [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Loewy, Rachel L.; Stuart, Barbara K.; Vinogradov, Sophia; Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Perez, Veronica B.; Ford, Judith M.; Roach, Brian J.; Vinogradov, Sophia; Mathalon, Daniel H.] San Francisco Vet Adm Med Ctr, Dept Psychiat, San Francisco, CA USA. RP Mathalon, DH (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. EM daniel.mathalon@ucsf.edu OI Roach, Brian/0000-0002-3264-1465; Mathalon, Daniel/0000-0001-6090-4974 FU National Institutes of Health [R01MH076989, K02MH067967] FX National Institutes of Health (R01MH076989, K02MH067967). NR 40 TC 7 Z9 7 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2012 VL 38 IS 6 BP 1216 EP 1224 DI 10.1093/schbul/sbr124 PG 9 WC Psychiatry SC Psychiatry GA 035KD UT WOS:000310944500017 PM 21993915 ER PT J AU Cornblatt, BA Carrion, RE Addington, J Seidman, L Walker, EF Cannon, TD Cadenhead, KS McGlashan, TH Perkins, DO Tsuang, MT Woods, SW Heinssen, R Lencz, T AF Cornblatt, Barbara A. Carrion, Ricardo E. Addington, Jean Seidman, Larry Walker, Elaine F. Cannon, Tyronne D. Cadenhead, Kristin S. McGlashan, Thomas H. Perkins, Diana O. Tsuang, Ming T. Woods, Scott W. Heinssen, Robert Lencz, Todd TI Risk Factors for Psychosis: Impaired Social and Role Functioning SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical high risk; functional deficits; prodromal; social risk factors; functional outcome; attenuated positive symptoms ID CLINICAL HIGH-RISK; 2ND-GENERATION ANTIPSYCHOTICS; NEUROCOGNITIVE DEFICITS; SCHIZOPHRENIA PRODROME; NEGATIVE SYMPTOMS; ADOLESCENTS; INDIVIDUALS; PERFORMANCE; REHABILITATION; COMPETENCE AB Objectives: Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Methods: Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. Results: At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Conclusions: Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability. C1 [Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY 11004 USA. [Cornblatt, Barbara A.; Lencz, Todd] Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. [Cornblatt, Barbara A.; Carrion, Ricardo E.; Lencz, Todd] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA. [Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Seidman, Larry] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div,Beth Israel Deaco, Boston, MA 02115 USA. [Seidman, Larry] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Cannon, Tyronne D.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA USA. [Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Cornblatt, BA (reprint author), N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Div Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM Cornblat@lij.edu RI Lencz, Todd/J-3418-2014; OI Lencz, Todd/0000-0001-8586-338X; Carrion, Ricardo/0000-0002-6393-392X FU National Institute of Mental Health [R01 MH061523, U01 MH081857, R18 MH43518, U01 MH081928, P50 MH080272, R01 MH65079, RO1 MH062066, 5U01 MH081988, R01 MH60720, K24 MH76191, K05 MH01654, U01 MH066069, P50 MH064065, U01 MH74356, U01 MH082022, R41 MH083436, U01 MH066134]; Eli Lilly; Merck; Clinical Data Inc.; GoldenHelix, Inc.; Guidepoint Global; Cowen Co; Janssen Pharmaceuticals; Dainippon Sumitomo Pharma; AstraZeneca Pharmaceuticals; Bristol-Myers Squibb; Otsuka Pharmaceutical Co Ltd; Eli Lilly and Company; Pfizer; GlaxoSmithKline; Forest Labs; Shire; UCB Pharma; Bristol- Myers Squibb FX National Institute of Mental Health (R01 MH061523, U01 MH081857 to Dr B.A.C.; R18 MH43518, U01 MH081928, P50 MH080272 to Dr L.S.; R01 MH65079 to Dr T.D.C.; RO1 MH062066, 5U01 MH081988 to Dr E.F.W.; R01 MH60720, K24 MH76191 to Dr K.S.C.; K05 MH01654 to Dr T.H.M.; U01 MH066069, P50 MH064065 to Dr D.O.P.; R18 MH43518 to Dr M.T.; U01 MH74356, U01 MH082022, R41 MH083436 to Dr S.W.W.; and U01 MH066134 to Dr J.A.).; We thank the study participants for their time and effort. We also thank Jennifer Johnson, PhD (UCLA), Diane Kirsopp, BA (University of Toronto), and Roy Money, MS (Yale University) for their contributions to the NAPLS I database described in this article. The authors also thank Andrea Auther, PhD, Lauren Baskir, PhD, and Ruth Olsen, BS. Conflict of interest: Dr. Cornblatt was the original developer of the CPT-IP and has been an advisor for Bristol-Myers Squibb and Merck. Dr. Lencz has received consulting fees and/or honoraria from Eli Lilly, Merck, Clinical Data Inc., GoldenHelix, Inc., Guidepoint Global, and Cowen & Co. Dr. Carrion has not received funding from for-profit entities. Dr. Seidman has not received funding from for-profit entities in the past 12 months. In the past he received unrestricted educational support from Janssen Pharmaceuticals and has served as a consultant for Shire. Dr. Walker has not received funding from for-profit entities. Dr. Cannon has served as a consultant for Janssen Pharmaceuticals and Eli Lilly and Company. Dr. Cadenhead has not received funding from for-profit entities. Dr. McGlashan has served as a consultant for Eli Lilly and Company, Pfizer, Solvay/Wyeth, and Roche Pharmaceuticals. Dr. Perkins has received research funding from Janssen Pharmaceuticals and Dainippon Sumitomo Pharma in the past 12 months. In the past Dr. Perkins received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Otsuka Pharmaceutical Co Ltd, Eli Lilly and Company, Janssen Pharmaceuticals, and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly and Company, Janssen Pharmaceuticals, GlaxoSmithKline, Forest Labs, Pfizer, and Shire. Dr. Tsuang has received research grants from Janssen Pharmaceuticals. Dr. Woods has received research funding support from multiple for-profit entities including UCB Pharma and Bristol- Myers Squibb and has consulted for Otsuka and Schering-Plough. Dr Woods has not served on speaker's bureaus. Dr. Heinssen is an employee of the nonprofit National Institutes of Health and has had no financial relationships with for-profit entities. Dr. Addington has served as a consultant for Pfizer, AstraZeneca Pharmaceuticals, and Janssen Pharmaceuticals. NR 44 TC 59 Z9 58 U1 7 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2012 VL 38 IS 6 BP 1247 EP 1257 DI 10.1093/schbul/sbr136 PG 11 WC Psychiatry SC Psychiatry GA 035KD UT WOS:000310944500020 PM 22080497 ER PT J AU Williams, ME Sandeep, J Catic, A AF Williams, Mark E. Sandeep, Jeena Catic, Angela TI Aging and ESRD Demographics: Consequences for the Practice of Dialysis SO SEMINARS IN DIALYSIS LA English DT Article ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; HEMODIALYSIS-PATIENTS; MORTALITY RISK; PREVALENCE; OUTCOMES; AGE; POPULATION; SURVIVAL AB The disproportionate increase in the prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in the elderly is now recognized as a national and global reality. Among the major contributing factors are the aging of the population, a growing prevalence of CKD, greater access to care, and increased comorbidities. The utilization of renal replacement therapy in the geriatric population has concomitantly increased. It is imposing enormous challenges to the practice of ESRD care, the largest of which may be to determine the best application of clinical performance targets to a population with limitations in life expectancy. Concurrently, increased focus on quality of life will be required. The effective dialysis practitioner will need to adapt to the aging ESRD demographics with an increased focus on physical and mental well-being of the geriatric patient. C1 [Williams, Mark E.; Catic, Angela] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sandeep, Jeena] Mt Auburn Hosp, Cambridge, MA USA. RP Williams, ME (reprint author), Beth Israel Deaconess Med Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM mwillia5@bidmc.harvard.edu NR 38 TC 5 Z9 5 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD NOV-DEC PY 2012 VL 25 IS 6 BP 617 EP 622 DI 10.1111/sdi.12029 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 041LX UT WOS:000311404400005 PM 23067122 ER PT J AU Falcone, GJ Biffi, A Devan, WJ Jagiella, JM Schmidt, H Kissela, B Hansen, BM Jimenez-Conde, J Giralt-Steinhauer, E Elosua, R Cuadrado-Godia, E Soriano, C Ayres, AM Schwab, K Pera, J Urbanik, A Rost, NS Goldstein, JN Viswanathan, A Pichler, A Enzinger, C Norrving, B Tirschwell, DL Selim, M Brown, DL Silliman, SL Worrall, BB Meschia, JF Kidwell, CS Montaner, J Fernandez-Cadenas, I Delgado, P Broderick, JP Greenberg, SM Roquer, J Lindgren, A Slowik, A Schmidt, R Flaherty, ML Kleindorfer, DO Langefeld, CD Woo, D Rosand, J AF Falcone, Guido J. Biffi, Alessandro Devan, William J. Jagiella, Jeremiasz M. Schmidt, Helena Kissela, Brett Hansen, Bjoern M. Jimenez-Conde, Jordi Giralt-Steinhauer, Eva Elosua, Roberto Cuadrado-Godia, Elisa Soriano, Carolina Ayres, Alison M. Schwab, Kristin Pera, Joanna Urbanik, Andrzej Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Pichler, Alexander Enzinger, Christian Norrving, Bo Tirschwell, David L. Selim, Magdy Brown, Devin L. Silliman, Scott L. Worrall, Bradford B. Meschia, James F. Kidwell, Chelsea S. Montaner, Joan Fernandez-Cadenas, Israel Delgado, Pilar Broderick, Joseph P. Greenberg, Steven M. Roquer, Jaume Lindgren, Arne Slowik, Agnieszka Schmidt, Reinhold Flaherty, Matthew L. Kleindorfer, Dawn O. Langefeld, Carl D. Woo, Daniel Rosand, Jonathan CA Int Stroke Genetics Consortium TI Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage SO STROKE LA English DT Article DE genetic risk score; genetics; hypertension; intracerebral hemorrhage ID GENOME-WIDE ASSOCIATION; BLOOD-PRESSURE; DISEASE RISK; POPULATION; STROKE; PATHOPHYSIOLOGY; VALIDATION; VARIANTS; GENOTYPE; SEQUENCE AB Background and Purpose-Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (single nucleotide polymorphisms [SNPs]) associated with blood pressure levels have been identified. We sought to determine whether the cumulative burden of blood pressure-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods-We conducted a prospective multicenter case-control study in 2272 subjects of European ancestry (1025 cases and 1247 control subjects). Thirty-nine SNPs reported to be associated with blood pressure levels were identified from the National Human Genome Research Institute genomewide association study catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results-No single SNP was associated with either ICH or pre-ICH HTN. The blood pressure-based unweighted genetic risk score was associated with risk of ICH (OR, 1.11; 95% CI, 1.02-1.21; P=0.01) and the subset of ICH in deep regions (OR, 1.18; 95% CI, 1.07-1.30; P=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among control subjects (OR, 1.17; 95% CI, 1.04-1.31; P=0.009) and ICH cases (OR, 1.15; 95% CI, 1.01-1.31; P=0.04). Similar results were obtained when using a weighted score. Conclusion-Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. (Stroke. 2012; 43: 2877-2883.) C1 [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Ayres, Alison M.; Schwab, Kristin; Rost, Natalia S.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Rost, Natalia S.; Viswanathan, Anand; Greenberg, Steven M.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Falcone, Guido J.; Biffi, Alessandro; Devan, William J.; Rost, Natalia S.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Falcone, Guido J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Jagiella, Jeremiasz M.; Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Urbanik, Andrzej] Jagiellonian Univ, Coll Med, Dept Radiol, Krakow, Poland. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Med Biochem, Graz, Austria. [Kissela, Brett; Broderick, Joseph P.; Flaherty, Matthew L.; Kleindorfer, Dawn O.; Woo, Daniel] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA. [Hansen, Bjoern M.; Norrving, Bo; Lindgren, Arne] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Hansen, Bjoern M.; Norrving, Bo; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Cuadrado-Godia, Elisa; Soriano, Carolina; Roquer, Jaume] Univ Autonoma Barcelona, Hosp del Mar, Dept Neurol, Neurovasc Res Unit, E-08193 Barcelona, Spain. [Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina] Univ Autonoma Barcelona, Hosp del Mar, Program Inflammat & Cardiovasc Disorders, Inst Municipal Invest Med, E-08193 Barcelona, Spain. [Pichler, Alexander; Enzinger, Christian; Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria. [Enzinger, Christian] Med Univ Graz, Dept Radiol, Neuroradiol Sect, Graz, Austria. [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Stroke Ctr, Seattle, WA 98104 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Dept Neurol, Stroke Program, Ann Arbor, MI USA. [Silliman, Scott L.] Univ Florida, Coll Med, Dept Neurol, Jacksonville, FL USA. [Worrall, Bradford B.] Univ Virginia Hlth Syst, Dept Neurol & Publ Hlth Sci, Charlottesville, VA USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Kidwell, Chelsea S.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Res Lab, E-08193 Barcelona, Spain. [Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar] Univ Autonoma Barcelona, Hosp Vall dHebron, Inst Recerca, Neurovasc Unit, E-08193 Barcelona, Spain. [Langefeld, Carl D.] Wake Forest Univ, Dept Biostat Sci, Winston Salem, NC 27109 USA. RP Rosand, J (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM jrosand@partners.org RI JIMENEZ-CONDE, JORDI/C-1941-2012; Montaner, Joan/D-3063-2015; Goldstein, Joshua/H-8953-2016; IBIS, NEUROVASCULAR/O-1855-2015; Falcone, Guido/L-2287-2016; OI Falcone, Guido/0000-0002-6407-0302; Hansen, Bjorn/0000-0001-8661-9063; Brown, Devin/0000-0002-9815-3421; ELOSUA, ROBERTO/0000-0001-8235-0095; Norrving, Bo/0000-0002-8024-5096; Ayres, Alison/0000-0002-5492-1695; Kissela, Brett/0000-0002-9773-4013 FU National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) [5U54NS057405, R01NS059727]; National Institutes of Health [NS36695, NS30678]; Greater Cincinnati Foundation; Keane Stroke Genetics Research Fund; Edward and Maybeth Sonn Research Fund; University of Michigan General Clinical Research Center [M01 RR000042]; National Center for Research Resources; American Heart Association/Bugher Foundation Centers for Stroke Prevention Research [0775010N]; Hospital del Mar ICH study: Ministerio de Sanidad y Consumo de Espana, Instituto de Salud Carlos III [PI051737, PI10/02064, RD06/0009]; polish Ministry of Education; Lund University; Region Skane; Swedish Research Council [K2010-61X-20378-04-3]; Freemasons Lodge of Instruction EOS in Lund; King Gustav V Foundation; Queen Victoria's Foundation; Department of Neurology Lund; Swedish Stroke Association; Austrian Science Fond (FWF) [P20545-P05, P13180]; [N N402 083934] FX This study is funded by National Institutes of Health-National Institute of Neurological Disorders and Stroke (NIH-NINDS) grant 5U54NS057405 (Differences in the Imaging of Primary Hemorrhage Based on Ethnicity or Race [DECIPHER]), Genetic and Environmental Risk Factors for Hemorrhagic Stroke. This study was supported by National Institutes of Health grants NS36695 (Genetic and Environmental Risk Factors for Hemorrhagic Stroke) and NS30678 (Hemorrhagic and Ischemic Stroke Among Blacks and Whites) and by the Greater Cincinnati Foundation Grant (Cincinnati Control Cohort), Genetics of Cerebral Hemorrhage on Anticoagulation. This study was funded by NIH-NINDS grants R01NS059727, the Keane Stroke Genetics Research Fund, the Edward and Maybeth Sonn Research Fund, by the University of Michigan General Clinical Research Center (M01 RR000042), and by a grant from the National Center for Research Resources. Drs Biffi and Anderson were supported in part by the American Heart Association/Bugher Foundation Centers for Stroke Prevention Research (0775010N), Hospital del Mar ICH study: Ministerio de Sanidad y Consumo de Espana, Instituto de Salud Carlos III with the grants: "Registro BASICMAR" Funding for Research in Health (PI051737); "GWALA project (PI10/02064)"; Grant from Spanish Research Networks "Red HERACLES" (RD06/0009). Jagiellonian University Hemorrhagic Stroke Study: This study is supported by a grant funded by the Polish Ministry of Education (N N402 083934). Lund Stroke Register: Lund University, Region Skane, the Swedish Research Council (K2010-61X-20378-04-3), the Freemasons Lodge of Instruction EOS in Lund, King Gustav V and Queen Victoria's Foundation, Lund University, the Department of Neurology Lund, and the Swedish Stroke Association. Biobank services and genotyping were performed at Region Skane Competence Centre (RSKC Malmo), Skane University Hospital, Malmo, Sweden. Medical University of Graz ICH Study: control subjects of the MUG-ICH study are from the Austrian Stroke Prevention Study (ASPS), a population-based study funded by the Austrian Science Fond (FWF) grant numbers P20545-P05 and P13180. The Medical University of Graz supports the databank of the ASPS. All funding entities had no involvement in study design, data collection, analysis, and interpretation, writing of the report and in the decision to submit the paper for publication. NR 31 TC 15 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 2877 EP U183 DI 10.1161/STROKEAHA.112.659755 PG 15 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800270 PM 22933587 ER PT J AU Cheng, B Ebinger, M Kufner, A Koehrmann, M Wu, O Kang, DW Liebeskind, D Tourdias, T Singer, OC Christensen, S Warach, S Luby, M Fiebach, JB Fiehler, J Gerloff, C Thomalla, G AF Cheng, Bastian Ebinger, Martin Kufner, Anna Koehrmann, Martin Wu, Ona Kang, Dong-Wha Liebeskind, David Tourdias, Thomas Singer, Oliver C. Christensen, Soren Warach, Steve Luby, Marie Fiebach, Jochen B. Fiehler, Jens Gerloff, Christian Thomalla, Goetz CA Stroke Imaging Repository STIR TI Hyperintense Vessels on Acute Stroke Fluid-Attenuated Inversion Recovery Imaging Associations With Clinical and Other MRI Findings SO STROKE LA English DT Article DE acute stroke; diffusion-weighted; fluid-attenuated inversion recovery; magnetic resonance imaging; stroke ID FLAIR MRI; ABNORMALITIES; TRIAL AB Background and Purpose-Hyperintense vessels (HVs) have been observed in fluid-attenuated inversion recovery imaging of patients with acute ischemic stroke and been linked to slow flow in collateral arterial circulation. Given the potential importance of HV, we used a large, multicenter data set of patients with stroke to clarify which clinical and imaging factors play a role in HV. Methods-We analyzed data of 516 patients from the previously published PRE-FLAIR study (PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients <= 3 and <= 4.5 hours of symptom onset-a multicenter study) study. Patients were studied by MRI within 12 hours of symptom onset. HV were defined as hyperintensities in fluid-attenuated inversion recovery corresponding to the typical course of a blood vessel that was not considered the proximal, occluded main artery ipsilateral to the diffusion restriction. Presence of HV was rated by 2 observers and related to clinical and imaging findings. Results-Presence of HV was identified in 240 of all 516 patients (47%). Patients with HV showed larger initial ischemic lesion volumes (median, 12.3 versus 4.9 mL; P<0.001) and a more severe clinical impairment (median National Institutes of Health Stroke Scale 10.5 versus 6; P<0.001). In 198 patients with MR angiography, HVs were found in 80% of patients with vessel occlusion and in 17% without vessel occlusion. In a multivariable logistic regression model, vessel occlusion was associated with HV (OR, 21.7%; 95% CI, 9.6-49.9; P<0.001). HV detected vessel occlusion with a specificity of 0.86 (95% CI, 0.80-0.90) and sensitivity of 0.76 (95% CI, 0.69-0.83). Conclusions-HVs are a common finding associated with proximal arterial occlusions and more severe strokes. HVs predict arterial occlusion with high diagnostic accuracy. (Stroke. 2012;43:2957-2961.) C1 [Cheng, Bastian; Gerloff, Christian; Thomalla, Goetz] Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, D-20246 Hamburg, Germany. [Ebinger, Martin; Kufner, Anna; Fiebach, Jochen B.] Charite, Centrum Schlaganfallforsch, D-13353 Berlin, Germany. [Koehrmann, Martin] Univ Erlangen Nurnberg, Neurol Klin, Erlangen, Germany. [Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol,Med Sch, Boston, MA USA. [Kang, Dong-Wha] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Liebeskind, David] Univ Calif, Dept Neurol, Oakland, CA USA. [Tourdias, Thomas] Univ Bordeaux, Serv NeuroImagerie Diagnost Therapeut, Bordeaux, France. [Singer, Oliver C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neuroradiol, Erlangen, Germany. [Christensen, Soren] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia. [Warach, Steve; Luby, Marie] NINDS, Bethesda, MD 20892 USA. Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neuroradiol Diagnost & Intervent, D-20246 Hamburg, Germany. RP Cheng, B (reprint author), Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Neurol, Kopf & Neurozentrum, Martinistr 52, D-20246 Hamburg, Germany. EM b.cheng@uke.uni-hamburg.de OI Fiebach, Jochen B./0000-0002-7936-6958 FU Boehringer Ingelheim; Lundbeck; Siemens; Syngis; Synarc; Bayer Vital; EBS Technologies; Glaxo Smith Kline; Pfizer; Sanofi Aventis; Silk Road Medical; UCB; CoAxia; Concentric Medical, Inc.; Else Kro-ner-Fresenius-Stiftung; French Government (PHRC); National Institutes of Health [R01NS059775, R01NS063925, P50NS051343]; GE; Olea; Imaging Biometrics; National Institute of Neurological Disorders and Stroke (NINDS); Else-Kroner-Fresenius-Stiftung [2009_A36]; Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin [01 EO 0801]; European Union [202213, 223153]; Volkswagen Foundation; Deutsche Forschungsgemeinschaft; National Health and Medical Research Council (Australia); National Stroke Foundation (Australia); Heart Foundation of Australia; French national grant "Le programme hospitalier de recherche Clinique" (PHRC) FX J.B.F. has received fees as a board member, consultant, or lecturer from Boehringer Ingelheim, Lundbeck, Siemens, Syngis, and Synarc. C.G. has received fees as a consultant or lecture fees from Bayer Vital, Boehringer Ingelheim, EBS Technologies, Glaxo Smith Kline, Lundbeck, Pfizer, Sanofi Aventis, Silk Road Medical, and UCB. D.L. has received fees as a consultant for CoAxia and Concentric Medical, Inc. G.T. has received a research grant from the Else Kro-ner-Fresenius-Stiftung. T.T. has received a national grant from the French Government (PHRC). O.W. was supported in part by grants from the National Institutes of Health (R01NS059775, R01NS063925, P50NS051343) and received royalties and licensing fees from GE, Olea, and Imaging Biometrics.; This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS). The PREdictive value of FLAIR and DWI for the identification of acute ischemic stroke patients <= 3 and <= 4.5 h of symptom onset-a multicenter study (PRE-FLAIR) has received funding from the Else-Kroner-Fresenius-Stiftung (2009_A36). In Berlin, data were collected within the 1000+ study, which has received funding from the Federal Ministry of Education and Research via the grant Center for Stroke Research Berlin (01 EO 0801). This work was further supported by the European Union's Seventh Framework Programme grant agreement No. 202213 and No 223153 (European Stroke Network), the Volkswagen Foundation, and the Deutsche Forschungsgemeinschaft. Echoplanar Imaging Thrombolysis Evaluation Trial (EPITHET) was a Phase II prospective, randomized, double-blinded, placebo-controlled, multinational trial funded by the National Health and Medical Research Council (Australia), the National Stroke Foundation (Australia), and the Heart Foundation of Australia. Valeur predictive des parametres IRM a la phase aigue de l'accident vasculaire cerebral: application a la gestion des essaistherapeutiques (VIRAGE) is a national multicentre study supported by French national grant "Le programme hospitalier de recherche Clinique" (PHRC). NR 17 TC 16 Z9 23 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 2957 EP 2961 DI 10.1161/STROKEAHA.112.658906 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800282 PM 22933582 ER PT J AU Hu, XM Li, PY Guo, YL Wang, HY Leak, RK Chen, SE Gao, YQ Chen, J AF Hu, Xiaoming Li, Peiying Guo, Yanling Wang, Haiying Leak, Rehana K. Chen, Songela Gao, Yanqin Chen, Jun TI Microglia/Macrophage Polarization Dynamics Reveal Novel Mechanism of Injury Expansion After Focal Cerebral Ischemia SO STROKE LA English DT Article DE inflammation macrophage; microglia; phagocytosis; polarization; stroke ID MACROPHAGE POLARIZATION; GENE-EXPRESSION; SPINAL-CORD; MICROGLIA; BRAIN; INFLAMMATION; ACTIVATION; RESPONSES; MOUSE; CELLS AB Background and Purpose-Mononuclear phagocytes are highly plastic cells that assume diverse phenotypes in response to microenvironmental signals. The phenotype-specific roles of microglia/macrophages in ischemic brain injury are poorly understood. A comprehensive characterization of microglia/macrophage polarization after ischemia may advance our knowledge of poststroke damage/recovery. Methods-Focal transient cerebral ischemia was induced in mice for 60 minutes; animals were euthanized at 1 to 14 days of reperfusion. Reverse-transcriptase polymerase chain reaction and immunohistochemical staining for M1 and M2 markers were performed to characterize phenotypic changes in brain cells, including microglia and infiltrating macrophages. In vitro experiments using a transwell system, a conditioned medium transfer system, or a coculture system allowing cell-to-cell contacts were used to further elucidate the effect of neuronal ischemia on microglia/macrophage polarization and, conversely, the effect of microglia/macrophage phenotype on the fate of ischemic neurons. Results-Local microglia and newly recruited macrophages assume the M2 phenotype at early stages of ischemic stroke but gradually transformed into the M1 phenotype in peri-infarct regions. In vitro experiments revealed that ischemic neurons prime microglial polarization toward M1 phenotype. M1-polarized microglia or M1-conditioned media exacerbated oxygen glucose deprivation-induced neuronal death. In contrast, maintaining the M2 phenotype of microglia protected neurons against oxygen glucose deprivation. Conclusions-Our results suggest that microglia/macrophages respond dynamically to ischemic injury, experiencing an early "healthy" M2 phenotype, followed by a transition to a "sick" M1 phenotype. These dual and opposing roles of microglia/macrophages suggest that stroke therapies should be shifted from simply suppressing microglia/macrophage toward adjusting the C1 [Hu, Xiaoming; Li, Peiying; Wang, Haiying; Chen, Songela; Chen, Jun] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Li, Peiying; Wang, Haiying; Chen, Songela; Chen, Jun] Univ Pittsburgh, Ctr Cerebrovasc Dis Res, Pittsburgh, PA 15213 USA. [Hu, Xiaoming; Li, Peiying; Guo, Yanling; Gao, Yanqin; Chen, Jun] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. [Hu, Xiaoming; Li, Peiying; Guo, Yanling; Gao, Yanqin; Chen, Jun] Fudan Univ, Inst Brain Sci, Shanghai 200433, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15219 USA. [Leak, Rehana K.] Duquesne Univ, Mylan Sch Pharm, Pittsburgh, PA 15219 USA. [Chen, Jun] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. EM hux2@upmc.edu; chenj2@upmc.edu RI Gao, Yanqin/I-6790-2016; OI Gao, Yanqin/0000-0002-4915-9819; Leak, Rehana/0000-0003-2817-7417 FU National Institutes of Health [NS045048, NS36736, NS43802, NS56118]; American Heart Association [10POST4150028]; Chinese Natural Science Foundation [30870794] FX This project was supported by National Institutes of Health grants to J.C. (NS045048, NS36736, NS43802, and NS56118), a grant from the American Heart Association to X.H (10POST4150028), and Chinese Natural Science Foundation grants to Y. Gao. (30870794). NR 27 TC 253 Z9 255 U1 17 U2 71 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 3063 EP U474 DI 10.1161/STROKEAHA.112.659656 PG 11 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800300 PM 22933588 ER PT J AU Gan, Y Xing, J Jing, Z Stetler, RA Zhang, F Luo, YM Ji, XM Gao, YQ Cao, GD AF Gan, Yu Xing, Juan Jing, Zheng Stetler, R. Anne Zhang, Feng Luo, Yumin Ji, Xunming Gao, Yanqin Cao, Guodong TI Mutant Erythropoietin Without Erythropoietic Activity Is Neuroprotective Against Ischemic Brain Injury SO STROKE LA English DT Article DE AKT; cerebral ischemia; ERK1/2; erythropoietin; erythropoietin mutant; neuroprotection; neurotoxicity ID CEREBRAL-ISCHEMIA; IN-VIVO; PROTECTS; ASIALOERYTHROPOIETIN; NEURONS AB Background and Purpose-Erythropoietin (EPO) confers potent neuroprotection against ischemic injury. However, treatment for stroke requires high doses and multiple administrations of EPO, which may cause deleterious side effects due to its erythropoietic activity. This study identifies a novel nonerythropoietic mutant EPO and investigates its potential neuroprotective effects and underlying mechanism in an animal model of cerebral ischemia. Methods-We constructed a series of mutant EPOs, each containing a single amino acid mutation within the erythropoietic motif, and tested their erythropoietic activity. Using cortical neuronal cultures exposed to -N--methyl--d--aspartate neurotoxicity and a murine model of transient middle cerebral artery occlusion, neuroprotection and neurofunctional outcomes were assessed as well as activation of intracellular signaling pathways. Results-The serine to isoleucine mutation at position 104 (S104I-EPO) completely abolished the erythropoietic and -platelet--stimulating activity of EPO. Administration of S104-I--EPO significantly inhibited -N--methyl-d--aspartate--induced neuronal death in primary cultures and protected against cerebral infarction and neurological deficits with an efficacy similar to that of -wild--type EPO. Both S104-I--EPO and -wild--type EPO activated similar prosurvival signaling pathways such as phosphatidylinositol 3-kinase/AKT, -mitogen--activated protein kinase/extracellular -signal--regulated kinase 1/2, and STAT5. Inhibition of phosphatidylinositol 3-kinase/AKT or -mitogen--activated protein kinase/extracellular -signal-regulated kinase 1/2 signaling pathways significantly attenuated the neuroprotective effects of S104-I--EPO, indicating that activation of these pathways underlies the neuroprotective mechanism of mutant EPO against cerebral ischemia. Conclusions-S104-I--EPO confers neuroprotective effects comparable to those of -wild--type EPO against ischemic brain in-jury with the added benefit of lacking erythropoietic and -platelet--stimulating side effects. Our novel findings suggest that the nonerythropoietic mutant EPO is a legitimate candidate for ischemic stroke intervention. (Stroke. 2012; 43: 3071-3077.) C1 [Gan, Yu; Xing, Juan; Jing, Zheng; Stetler, R. Anne; Cao, Guodong] Univ Pittsburgh, Dept Neurol, Sch Med, Pittsburgh, PA 15260 USA. [Gan, Yu; Jing, Zheng; Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Luo, Yumin; Ji, Xunming] Capital Univ Med Sci, Xuanwu Hosp, Res Inst, Beijing, Peoples R China. [Stetler, R. Anne; Gao, Yanqin; Cao, Guodong] Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. RP Cao, GD (reprint author), Univ Pittsburgh, Dept Neurol, Sch Med, BST S505,3500 Terrace St, Pittsburgh, PA 15260 USA. EM caog@upmc.edu FU Department of Veteran's Affairs Merit Review grant 1I01RX000199; National Institutes of Health/National Institute of Neurological Disorders and Stroke [NS053473]; American Heart Association Scientist Development [06300064N] FX This project was supported by Department of Veteran's Affairs Merit Review grant 1I01RX000199 (to Dr Cao), National Institutes of Health/National Institute of Neurological Disorders and Stroke grant NS053473 (to Dr Cao), and American Heart Association Scientist Development Grant 06300064N (to Dr Cao). NR 15 TC 9 Z9 10 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP 3071 EP 3077 DI 10.1161/STROKEAHA.112.663120 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800301 PM 22984011 ER PT J AU Depta, JP Kottke-Marchant, K Bhatt, DL AF Depta, Jeremiah P. Kottke-Marchant, Kandice Bhatt, Deepak L. TI Response to Letter Regarding Article "Clinical Outcomes Using a Platelet Function-Guided Approach for Secondary Prevention in Patients With Ischemic Stroke or Transient Ischemic Attack" SO STROKE LA English DT Letter C1 [Depta, Jeremiah P.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Kottke-Marchant, Kandice] Cleveland Clin, Cleveland, OH 44106 USA. [Bhatt, Deepak L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Depta, JP (reprint author), Washington Univ, Sch Med, St Louis, MO 63130 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP E168 EP E168 DI 10.1161/STROKEAHA.112.673210 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800259 ER PT J AU Jagiella, JM Pera, J Slowik, A Viswanathan, A Greenberg, SM AF Jagiella, Jeremiasz M. Pera, Joanna Slowik, Agnieszka Viswanathan, Anand Greenberg, Steven M. TI Burden of Risk Alleles for Hypertension Increases Risk of Intracerebral Hemorrhage (vol 43, pg 2877, 2012) SO STROKE LA English DT Correction C1 [Jagiella, Jeremiasz M.; Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Viswanathan, Anand; Greenberg, Steven M.] Massachusetts Gen Hosp, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. RP Jagiella, JM (reprint author), Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP E171 EP E171 DI 10.1161/STR.0b013e318277ef90 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800262 ER PT J AU Lanthier, S Dubuc, V Gioia, LC Ferro, JM Calabrese, LH Putaala, J Strbian, D Frosch, M Guilbert, F Raymond, J Poppe, AY AF Lanthier, S. Dubuc, V Gioia, L. C. Ferro, J. M. Calabrese, L. H. Putaala, J. Strbian, D. Frosch, M. Guilbert, F. Raymond, J. Poppe, A. Y. TI The INTERnational study on primary angiitis of the central nervous system (INTERSPACE) SO STROKE LA English DT Meeting Abstract CT 3rd Canadian Stroke Congress CY SEP 29-OCT 02, 2012 CL Calgary, CANADA C1 [Lanthier, S.; Dubuc, V; Gioia, L. C.; Guilbert, F.; Raymond, J.; Poppe, A. Y.] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Ferro, J. M.] Hosp Santa Maria, Lisbon, Portugal. [Calabrese, L. H.] Cleveland Clin, Cleveland, OH 44106 USA. [Putaala, J.; Strbian, D.] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Frosch, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2012 VL 43 IS 11 BP E156 EP E156 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 028OV UT WOS:000310432800219 ER PT J AU Lindquist, KA Barrett, LF AF Lindquist, Kristen A. Barrett, Lisa Feldman TI A functional architecture of the human brain: emerging insights from the science of emotion SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID INTRINSIC CONNECTIVITY NETWORKS; ANTERIOR INSULA; COGNITIVE-PROCESSES; NEUROIMAGING DATA; RESTING-STATE; NEURAL BASIS; CORTEX; METAANALYSIS; MIND; SYSTEMS AB The 'faculty psychology' approach to the mind, which attempts to explain mental function in terms of categories that reflect modular 'faculties', such as emotions, cognitions, and perceptions, has dominated research into the mind and its physical correlates. In this paper, we argue that brain organization does not respect the commonsense categories belonging to the faculty psychology approach. We review recent research from the science of emotion demonstrating that the human brain contains broadly distributed functional networks that can each be re-described as basic psychological operations that interact to produce a range of mental states, including, but not limited to, anger, sadness, fear, disgust, and so on. When compared to the faculty psychology approach, this 'constructionist' approach provides an alternative functional architecture to guide the design and interpretation of experiments in cognitive neuroscience. C1 [Lindquist, Kristen A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Univ, Dept Psychiat, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Med Sch, Charlestown, MA 02129 USA. RP Lindquist, KA (reprint author), Univ N Carolina, Dept Psychol, 321 Davie Hall, Chapel Hill, NC 27599 USA. EM kristen.lindquist@unc.edu; l.barrett@neu.edu FU Harvard University Mind/Brain/Behavior Postdoctoral Fellowship; National Institute of Health Director's Pioneer Award [DP1OD003312] FX We thank Christy Wilson-Mendenhall for her comments on a previous draft of this manuscript and are especially grateful for her thoughts on the default network's role in conceptual processing. Preparation of this manuscript was supported by a Harvard University Mind/Brain/Behavior Postdoctoral Fellowship to K.L. and a National Institute of Health Director's Pioneer Award (DP1OD003312) to L.F.B. NR 81 TC 88 Z9 90 U1 13 U2 142 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD NOV PY 2012 VL 16 IS 11 BP 533 EP 540 DI 10.1016/j.tics.2012.09.005 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 042LY UT WOS:000311473900005 PM 23036719 ER PT J AU Beresin, EV Balon, R Coverdale, JH Roberts, LW AF Beresin, Eugene V. Balon, Richard Coverdale, John H. Roberts, Laura Weiss TI Challenges in Child and Adolescent Psychiatric Education SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID PRIMARY-CARE; COMPETENCES; PROGRAM C1 [Beresin, Eugene V.] Harvard Univ, Dept Psychiat, Mass Gen Hosp, Boston, MA 02115 USA. Univ Psychiat Centrum St Jozef, Detroit, MI USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Beresin, EV (reprint author), Harvard Univ, Dept Psychiat, Mass Gen Hosp, Boston, MA 02115 USA. EM eberesin@partners.org NR 19 TC 1 Z9 1 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2012 VL 36 IS 6 BP 429 EP 432 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 039KL UT WOS:000311244600001 PM 23154685 ER PT J AU Fox, GS Stock, S Briscoe, GW Beck, GL Horton, R Hunt, JI Liu, HY Rutter, AP Sexson, S Schlozman, SC Stubbe, DE Stuber, ML AF Fox, Geraldine S. Stock, Saundra Briscoe, Gregory W. Beck, Gary L. Horton, Rita Hunt, Jeffrey I. Liu, Howard Y. Rutter, Ashley Partner Sexson, Sandra Schlozman, Steven C. Stubbe, Dorothy E. Stuber, Margaret L. TI Improving Child and Adolescent Psychiatry Education for Medical Students: An Inter-Organizational Collaborative Action Plan SO ACADEMIC PSYCHIATRY LA English DT Article AB Objective: A new Child and Adolescent Psychiatry in Medical Education (CAPME) Task Force, sponsored by the Association for Directors of Medical Student Education in Psychiatry (ADMSEP), has created an inter-organizational partnership between child and adolescent psychiatry (CAP) educators and medical student educators in psychiatry. This paper outlines the task force design and strategic plan to address the long-standing dearth of CAP training for medical students. Method: The CAPME ADMSEP Task Force, formed in 2010, identified common challenges to teaching CAP among ADMSEP's CAPME Task Force members, utilizing focus-group discussions and a needs-assessment survey. The Task Force was organized into five major sections, with inter-organizational action plans to address identified areas of need, such as portable modules and development of benchmark CAP competencies. Results/Conclusion: The authors predict that all new physicians, regardless of specialty, will be better trained in CAP. Increased exposure may also improve recruitment into this underserved area. Academic Psychiatry 2012; 36:461-464 C1 [Fox, Geraldine S.] Univ IL, Dept Psychiat, Chicago, IL 60607 USA. [Stock, Saundra] Univ S Florida, Dept Psychiat, Tampa, FL USA. [Briscoe, Gregory W.] Eastern Virginia Med Sch, Dept Psychiat, Hampton, VA USA. [Beck, Gary L.] Univ Nebraska Med Ctr, Omaha, NE USA. [Horton, Rita] LSUHSC, Dept Psychiat, Shreveport, LA USA. [Hunt, Jeffrey I.] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. [Liu, Howard Y.] UNMC, Dept Psychiat, Omaha, NE USA. [Rutter, Ashley Partner] AACAP, Washington, DC USA. [Sexson, Sandra] Georgia Hlth Sci, Dept Psychiat & Behav Sci, Augusta, GA USA. [Schlozman, Steven C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Stubbe, Dorothy E.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. [Stuber, Margaret L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Fox, GS (reprint author), Univ IL, Dept Psychiat, Chicago, IL 60607 USA. EM foxg@uic.edu NR 10 TC 3 Z9 3 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2012 VL 36 IS 6 BP 461 EP 464 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 039KL UT WOS:000311244600008 PM 23154693 ER PT J AU Sidhu, SS Chandra, RM AF Sidhu, Shawn Singh Chandra, Rohit M. TI Doing Data-Driven Research in Training: The Experience of Two Residents SO ACADEMIC PSYCHIATRY LA English DT Letter C1 [Sidhu, Shawn Singh] Univ Calif Los Angeles, Dept Child & Adolescent Psychiat, Los Angeles, CA 90095 USA. [Chandra, Rohit M.] Massachusetts Gen Hosp, Dept Child & Adolescent Psychiat, Boston, MA 02114 USA. RP Sidhu, SS (reprint author), Univ Calif Los Angeles, Dept Child & Adolescent Psychiat, Los Angeles, CA 90095 USA. EM shawnsidhu@yahoo.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD NOV-DEC PY 2012 VL 36 IS 6 BP 496 EP 496 PG 1 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 039KL UT WOS:000311244600018 PM 23154705 ER PT J AU Fan, XX Zhou, YF Liu, X Li, LF Su, XD AF Fan, Xue-Xin Zhou, Yan-Feng Liu, Xiang Li, Lan-Fen Su, Xiao-Dong TI Ellman's reagent in promoting crystallization and structure determination of Anabaena CcbP SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID HETEROCYST DIFFERENTIATION; PROTEIN; UROCANASE; BINDING AB Obtaining crystals presented a bottleneck in the structural study of Anabaena cyanobacterial Ca2+-binding protein (CcbP). In this report, the promoting effect of Ellman's reagent [5,5'-dithiobis(2-nitrobenzoic acid); DTNB] on the crystallization of CcbP is described. CcbP contains one free cysteine. A quick and simple oxidation reaction with DTNB blocked the free cysteine in purified CcbP and generated a homogenous monomeric protein for crystallization. The crystal structure of DTNB-modified CcbP was determined by the single-wavelength anomalous diffraction method. Structure analysis indicated that DTNB modification facilitated crystallization of CcbP by inducing polar interactions in the crystal lattice. DTNB-mediated cysteine modification was demonstrated to have little effect on the overall structure and the Ca2+ binding of CcbP. Thus, DTNB modification may provide a simple and general approach for protein modification to improve the success of crystallization screening. C1 [Fan, Xue-Xin; Li, Lan-Fen; Su, Xiao-Dong] Peking Univ, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China. [Fan, Xue-Xin; Li, Lan-Fen; Su, Xiao-Dong] Peking Univ, Biodynam Opt Imaging Ctr BIOPIC, Sch Life Sci, Beijing 100871, Peoples R China. [Zhou, Yan-Feng] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Liu, Xiang] Tianjin Int Joint Acad Biotechnol & Med, High Throughput Mol Drug Discovery Ctr, Tianjin 300457, Peoples R China. RP Su, XD (reprint author), Peking Univ, State Key Lab Prot & Plant Gene Res, 5 Yiheyuan Rd, Beijing 100871, Peoples R China. EM xdsu@pku.edu.cn FU Chinese Ministry of Science and Technology's National High Technology 973 Program [2011CB911103]; National Science Fund for Distinguished Young Scholars (NSFC) [30325012]; Chinese Ministry of Science and Technology's National High Technology 863 Program [2006AA02A317] FX We thank Drs Jie Nan and Xiao-Jun Wang for critical reading and discussion of the manuscript. This work was supported by a grant from the Chinese Ministry of Science and Technology's National High Technology 973 Program (2011CB911103). The National Science Fund for Distinguished Young Scholars (NSFC No. 30325012) and a grant from the Chinese Ministry of Science and Technology's National High Technology 863 Program (2006AA02A317) are acknowledged for supporting this work. NR 22 TC 0 Z9 1 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD NOV PY 2012 VL 68 BP 1409 EP 1414 DI 10.1107/S1744309112034938 PN 11 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 034OJ UT WOS:000310882500032 PM 23143261 ER PT J AU Patil, S Ma, A Lund, G Lund, K Shreffler, W AF Patil, S. Ma, A. Lund, G. Lund, K. Shreffler, W. TI Human basophils internalise antigen in an IgE-dependent fashion and express costimulatory molecules SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Patil, S.; Ma, A.; Shreffler, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lund, G.; Lund, K.] ALK Abello, Horsholm, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 129 BP 62 EP 63 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247700129 ER PT J AU Ruiter, B Grishina, G Jager, SD Knol, E Ozias-Akins, P Sampson, H Shreffler, W AF Ruiter, B. Grishina, G. Jager, den Hartog S. Knol, E. Ozias-Akins, P. Sampson, H. Shreffler, W. TI Human dendritic cells stimulated with a novel peanut protein express high levels of retinaldehyde dehydrogenase 2 and induce RA-sensitive genes in naive T-cells SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Ruiter, B.; Shreffler, W.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Grishina, G.; Sampson, H.] Mt Sinai Sch Med, New York, NY USA. [Jager, den Hartog S.; Knol, E.] Univ Med Ctr, Utrecht, Netherlands. [Ozias-Akins, P.] Univ Georgia, Dept Hort, Tifton, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 272 BP 120 EP 121 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247700262 ER PT J AU Ma, A Patil, S Matsui, E Shreffler, W AF Ma, A. Patil, S. Matsui, E. Shreffler, W. TI Algorithmic data analysis of mouse allergen activation of basophils and comparison to specific IgE and skin test sensitisation SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Ma, A.; Patil, S.; Shreffler, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Matsui, E.] Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 1426 BP 534 EP 535 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247703229 ER PT J AU Schneider, M Shreffler, W Jermann, T AF Schneider, M. Shreffler, W. Jermann, T. TI Evaluation of natural purified peanut allergens for the use in diagnosis with basophil activation test SO ALLERGY LA English DT Meeting Abstract CT 31st Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI) CY JUN 16-20, 2012 CL Geneva, SWITZERLAND SP European Acad Allergy & Clin Immunol (EAACI) C1 [Schneider, M.; Jermann, T.] BUHLMANN Labs AG, R&D Dept, Schoenenbuch, Switzerland. [Shreffler, W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 J9 ALLERGY JI Allergy PD NOV PY 2012 VL 67 SU 96 SI SI MA 1447 BP 542 EP 542 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 026CA UT WOS:000310247703250 ER PT J AU Durazzo, TC Insel, PS Weiner, MW AF Durazzo, Timothy C. Insel, Philip S. Weiner, Michael W. CA Alzheimer Dis Neuroimaging TI Greater regional brain atrophy rate in healthy elderly subjects with a history of cigarette smoking SO ALZHEIMERS & DEMENTIA LA English DT Article DE Alzheimer's disease; MRI; Brain volumes; Brain reward system; Cigarette smoking; Brain atrophy ID MAGNETIC-RESONANCE SPECTROSCOPY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; SMOKERS; NEUROBIOLOGY; ADDICTION; DEMENTIA; ALCOHOLISM; PATHOLOGY AB Background: Little is known about the effects of cigarette smoking on longitudinal brain morphological changes in the elderly. This study investigated the effects of a history of cigarette smoking on changes in regional brain volumes over 2 years in healthy, cognitively intact elderly individuals. We predicted that individuals with a history of cigarette smoking, compared with never smokers, demonstrate greater rate of atrophy over 2 years in regions that manifest morphological abnormalities in the early stages of Alzheimer's disease (AD), as well as in the extended brain reward/executive oversight system (BREOS), which is implicated in the development and maintenance of substance use disorders. Methods: Participants were healthy, cognitively normal elderly control subjects (75.9 +/- 4.8 years of age) with any lifetime history of cigarette smoking (n = 68) or no history of smoking (n = 118). Data were obtained through the Alzheimer Disease Neuroimaging Initiative from 2005 to 2010. Participants completed four magnetic resonance scans over 2 years. A standardized protocol using high-resolution three-dimensional T1-weighted sequences at 1.5 T was used for structural imaging and regional brain volumetric analyses. Results: Smokers demonstrated a significantly greater atrophy rate over 2 years than nonsmokers in multiple brain regions associated with the early stages of AD, as well as in the BREOS system. Groups did not differ on the rate of global cortical atrophy. Conclusions: A history of cigarette smoking in this healthy elderly cohort was associated with decreased structural integrity of multiple brain regions, which manifested as a greater rate of atrophy over 2 years in regions specifically affected by incipient AD as well as chronic substance abuse. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Durazzo, Timothy C.; Insel, Philip S.; Weiner, Michael W.] San Francisco VA Med Ctr, CIND, San Francisco, CA USA. [Durazzo, Timothy C.; Weiner, Michael W.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. RP Durazzo, TC (reprint author), San Francisco VA Med Ctr, CIND, San Francisco, CA USA. EM timothy.durazzo@ucsf.edu FU ADNI; National Institute on Aging [U01 AG024904]; National Institute of Biomedical Imaging and Bioengineering; National Institutes of Health [P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, K01 DA 024136]; Dana Foundation FX Data collection and sharing for this project was funded by the ADNI. ADNI is funded by the National Institute on Aging (U01 AG024904), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer, Inc., F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as nonprofit partners-the Alzheimer Association and Alzheimer Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org; http://www.fnih.org; http://www.fnih.org; http://www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer Disease Cooperative Study at the University of California, San Diego, CA. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles, CA. This research was also supported by National Institutes of Health grants P30 AG010129, K01 AG030514, R01 AG010897, R01 AG012435, K01 DA 024136; The Dana Foundation; and by resources and the use of facilities at the San Francisco Veterans Administration Medical Center, San Francisco, CA. T.C.D. and P.S.I. completed all statistical analyses. T.C.D., P.S.I., and M.W.W. were responsible for manuscript preparation. T.C.D. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. The authors thank the participants who made this research possible. NR 45 TC 19 Z9 20 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2012 VL 8 IS 6 BP 513 EP 519 DI 10.1016/j.jalz.2011.10.006 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 038KW UT WOS:000311174600007 PM 23102121 ER PT J AU Wild, KV Mattek, NC Maxwell, SA Dodge, HH Jimison, HB Kaye, JA AF Wild, Katherine V. Mattek, Nora C. Maxwell, Shoshana A. Dodge, Hiroko H. Jimison, Holly B. Kaye, Jeffrey A. TI Computer-related self-efficacy and anxiety in older adults with and without mild cognitive impairment SO ALZHEIMERS & DEMENTIA LA English DT Article DE Computer use; Mild cognitive impairment; Older adults ID CONTROLLED-TRIAL; INTERNET USAGE; TECHNOLOGY; ATTITUDES; HEALTH; WOMEN AB Background: This study examines differences in computer-related self-efficacy and anxiety in subgroups of older adults, and changes in those measures after exposure to a systematic training program and subsequent computer use. Methods: Participants were volunteers in the Intelligent Systems for Assessment of Aging Changes study (ISAAC) carried out by the Oregon Center for Aging and Technology. Participants were administered two questionnaires before training and again I year later, which were related to computer self-efficacy and anxiety. Continuous recording of computer use was also assessed for a subset of participants. Results: Baseline comparisons by sex, age, education, living arrangement, and computer proficiency, but not cognitive status, yielded significant differences in confidence and anxiety related to specific aspects of computer use. At 1-year follow-up, participants reported less anxiety and greater confidence. However, the benefits of training and exposure varied by group and task. Comparisons based on cognitive status showed that the cognitively intact participants benefited more from training and/or experience with computers than did participants with mild cognitive impairment (MCI), who after 1 year continued to report less confidence and more anxiety regarding certain aspects of computer use. Conclusion: After I year of consistent computer use, cognitively intact participants in this study reported reduced levels of anxiety and increased self-confidence in their ability to perform specific computer tasks. Participants with MCI at baseline were less likely to demonstrate increased efficacy or confidence than their cognitively intact counterparts. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Wild, Katherine V.; Mattek, Nora C.; Maxwell, Shoshana A.; Dodge, Hiroko H.; Jimison, Holly B.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. [Wild, Katherine V.; Mattek, Nora C.; Maxwell, Shoshana A.; Dodge, Hiroko H.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Jimison, Holly B.] Oregon Hlth & Sci Univ, Dept Med Informat & Clin Epidemiol, Portland, OR 97201 USA. [Kaye, Jeffrey A.] Portland VA Med Ctr, Neurol Serv, Portland, OR USA. RP Wild, KV (reprint author), Oregon Hlth & Sci Univ, Oregon Ctr Aging & Technol, Portland, OR 97201 USA. EM wildk@ohsu.edu OI Kaye, Jeffrey/0000-0002-9971-3478 FU National Institutes of Health [P30-AG008017, P30-AG024978, R01-AG024059, K01-AG23014]; Department of Veterans Affairs [P30-AG008017, M01-RR000334]; Intel Corporation FX This study was supported by National Institutes of Health grants P30-AG008017, P30-AG024978, R01-AG024059, and K01-AG23014; the Department of Veterans Affairs grants P30-AG008017 and M01-RR000334; and Intel Corporation. NR 29 TC 13 Z9 13 U1 1 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2012 VL 8 IS 6 BP 544 EP 552 DI 10.1016/j.jalz.2011.12.008 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 038KW UT WOS:000311174600011 PM 23102124 ER PT J AU Erten-Lyons, D Sherbakov, LO Piccinin, AM Hofer, SM Dodge, HH Quinn, JF Woltjer, RL Kramer, PL Kaye, JA AF Erten-Lyons, Deniz Sherbakov, Lena O. Piccinin, Andrea M. Hofer, Scott M. Dodge, Hiroko H. Quinn, Joseph F. Woltjer, Randy L. Kramer, Patricia L. Kaye, Jeffrey A. TI Review of selected databases of longitudinal aging studies SO ALZHEIMERS & DEMENTIA LA English DT Review DE Longitudinal study; Aging; Aged; Biomarkers; Database ID ALZHEIMERS-DISEASE AB One of the recommendations of the 2010 Leon Thal Symposium, organized to develop strategies to prevent Alzheimer's disease, was to build a global database of longitudinal aging studies. Although several databases of longitudinal aging studies exist, none of these are comprehensive or complete. In this article, we review selected databases of longitudinal aging studies. We also make recommendations on future steps to create a comprehensive database. Additionally, we discuss issues related to data harmonization. (C) 2012 The Alzheimer's Association. All rights reserved. C1 [Erten-Lyons, Deniz; Sherbakov, Lena O.; Dodge, Hiroko H.; Quinn, Joseph F.; Woltjer, Randy L.; Kramer, Patricia L.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Erten-Lyons, Deniz; Quinn, Joseph F.; Kaye, Jeffrey A.] Portland VA Med Ctr, Off Res & Dev, Portland, OR USA. [Piccinin, Andrea M.; Hofer, Scott M.] Univ Victoria, Dept Psychol, Victoria, BC, Canada. [Hofer, Scott M.] Univ Victoria, Ctr Aging, Victoria, BC, Canada. RP Erten-Lyons, D (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM ertenlyo@ohsu.edu RI Hofer, Scott/D-9090-2014; OI Hofer, Scott/0000-0001-8923-4337; Kaye, Jeffrey/0000-0002-9971-3478 FU Oregon Clinical and Translational Research Institute; National Center for Research Resources, a component of the NIH [UL1 RR024140]; NIH Road-map for Medical Research; Department of Veterans Affairs; NIH [AG08017] FX This publication was made possible with support from the Oregon Clinical and Translational Research Institute, grant number UL1 RR024140 from the National Center for Research Resources, a component of the NIH, and NIH Road-map for Medical Research; the Department of Veterans Affairs; and the NIH grant number AG08017. NR 15 TC 5 Z9 5 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD NOV PY 2012 VL 8 IS 6 BP 584 EP 589 DI 10.1016/j.jalz.2011.09.232 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 038KW UT WOS:000311174600016 PM 23102128 ER PT J AU Manzano-Fernandez, S Lopez-Cuenca, A Januzzi, JL Parra-Pallares, S Mateo-Martinez, A Sanchez-Martinez, M Perez-Berbel, P Orenes-Pinero, E Romero-Aniorte, AI Aviles-Plaza, F Valdes-Chavarri, M Marin, F AF Manzano-Fernandez, Sergio Lopez-Cuenca, Angel Januzzi, James L. Parra-Pallares, Soledad Mateo-Martinez, Alicia Sanchez-Martinez, Marianela Perez-Berbel, Patricio Orenes-Pinero, Esteban Romero-Aniorte, Ana I. Aviles-Plaza, Francisco Valdes-Chavarri, Mariano Marin, Francisco TI Usefulness of beta-Trace Protein and Cystatin C for the Prediction of Mortality in Non ST Segment Elevation Acute Coronary Syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; PROSTAGLANDIN-D-SYNTHASE; ARTERY-DISEASE; RENAL-FUNCTION; SERUM; CREATININE; OUTCOMES; MARKER; GAMMA; RISK AB Beta-trace protein (BTP) is a low-molecular mass protein belonging to the lipocalin protein family, which is more sensitive than serum creatinine for detecting impaired renal function. The aims of the present study were to evaluate whether plasma BTP improves the risk stratification of patients with non-ST-segment elevation acute coronary syndromes and to compare it to cystatin C (CysC), serum creatinine, and estimated glomerular filtration rate. Two hundred twenty-six consecutive patients with non-ST-segment elevation acute coronary syndromes were prospectively included. Blood samples were obtained within 24 hours of hospital admission to measure BTP, CysC, and creatinine. The study end point was all-cause death. Over a median follow-up period of 859 days (interquartile range [IQR] 524 to 1,164), 24 patients (10.6%) died. Decedents had higher concentrations of BTP (1.03 mg/L [IQR 0.89 to 1.43] vs 0.74 mg/L [IQR 0.61 to 0.92], p < 0.001), CysC (1.16 mg/L [IQR 0.91 to 1.59] vs 0.90 mg/L [IQR 0.76 to 1.08], p = 0.001), and serum creatinine (1.10 mg/L [IQR 0.87 to 1.46] vs 0.94 mg/L [IQR 0.80 to 1.10], p = 0.004) and a lower mean estimated glomerular filtration rate (60 +/- 20 vs 80 +/- 24 ml/min/1.73 m(2), p < 0.001). After multivariate adjustment, BTP and CysC were predictors of all-cause death, while estimated glomerular filtration rate and serum creatinine concentrations did not achieve statistical significance. In stratified analyses according to kidney function, elevated BTP and CysC were associated with a higher risk for all-cause death. Reclassification analyses showed that BTP and CysC added complementary information to Global Registry for Acute Coronary Events (GRACE) risk score. In conclusion, BTP and CysC levels were associated with all-cause death risk and modestly improved prognostic discrimination beyond the GRACE risk score in patients with non-ST segment elevation acute coronary syndromes. (c) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1240-1248) C1 [Manzano-Fernandez, Sergio; Lopez-Cuenca, Angel; Mateo-Martinez, Alicia; Sanchez-Martinez, Marianela; Orenes-Pinero, Esteban; Romero-Aniorte, Ana I.; Valdes-Chavarri, Mariano; Marin, Francisco] Univ Hosp Virgen de la Arrixaca, Div Cardiol, Murcia, Spain. [Parra-Pallares, Soledad; Aviles-Plaza, Francisco] Univ Hosp Virgen de la Arrixaca, Dept Biochem, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Perez-Berbel, Patricio] Univ Gen Hosp Alicante, Div Cardiol, Alicante, Spain. RP Manzano-Fernandez, S (reprint author), Univ Hosp Virgen de la Arrixaca, Div Cardiol, Murcia, Spain. EM sergiosmf13@hotmail.com FU Caja Murcia, Murcia, Spain [FFIS/CM09/016]; Murcia University, Murcia, Spain [Abbott/12399] FX This work was partially supported by research grant FFIS/CM09/016 from Caja Murcia, Murcia, Spain, and research grant Abbott/12399 from Murcia University, Murcia, Spain. NR 24 TC 11 Z9 13 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV PY 2012 VL 110 IS 9 BP 1240 EP 1248 DI 10.1016/j.amjcard.2012.06.027 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 036CG UT WOS:000311003400006 PM 22818840 ER PT J AU Ziegler, PD Glotzer, TV Daoud, EG Singer, DE Ezekowitz, MD Hoyt, RH Koehler, JL Coles, J Wyse, DG AF Ziegler, Paul D. Glotzer, Taya V. Daoud, Emile G. Singer, Daniel E. Ezekowitz, Michael D. Hoyt, Robert H. Koehler, Jodi L. Coles, James, Jr. Wyse, D. George TI Detection of Previously Undiagnosed Atrial Fibrillation in Patients With Stroke Risk Factors and Usefulness of Continuous Monitoring in Primary Stroke Prevention SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CLINICAL-SIGNIFICANCE; IMPLANTABLE DEVICES; EVENTS; ARRHYTHMIAS; WARFARIN; THERAPY; TACHYARRHYTHMIAS; DIAGNOSTICS; RATIONALE; ACCURACY AB The detection of undiagnosed atrial tachycardia/atrial fibrillation (AT/AF) among patients with stroke risk factors could be useful for primary stroke prevention. We analyzed newly detected AT/AF (NDAF) using continuous monitoring in patients with stroke risk factors but without previous stroke or evidence of AT/AF. NDAF (AT/AF > 5 minutes on any day) was determined in patients with implantable cardiac rhythm devices and >= 1 stroke risk factors (congestive heart failure, hypertension, age >= 75 years, or diabetes). All devices were capable of continuously monitoring the daily cumulative time in AT/AF. Of 1,368 eligible patients, NDAF was identified in 416(30%) during a follow-up of 1.1 +/- 0.7 years and was unrelated to the CHADS(2) score (congestive heart failure, hypertension [blood pressure consistently > 140/90 mm Hg or hypertension treated with medication], age >= 75 years, diabetes mellitus, previous stroke or transient ischemic attack). The presence of AT/AF > 6 hours on >= 1 day increased significantly with increased CHADS(2) scores and was present in 158 (54%) of 294 patients with NDAF and a CHADS(2) score of >= 2. NDAF was sporadic, and 78% of patients with a CHADS(2) score of >= 2 with NDAF experienced AT/AF on < 10% of the follow-up days. The median interval to NDAF detection in these higher risk patients was 72 days (interquartile range 13 to 177). In conclusion, continuous monitoring identified NDAF in 30% of patients with stroke risk factors. In patients with NDAF, AT/AF occurred sporadically, highlighting the difficulty in detecting paroxysmal AT/AF using traditional monitoring methods. However, AT/AF also persisted for > 6 hours on >= 1 days in most patients with NDAF and multiple stroke risk factors. Whether patients with CHADS(2) risk factors but without a history of AF might benefit from implantable monitors for the selection and administration of anticoagulation for primary stroke prevention merits additional investigation. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:1309-1314) C1 [Ziegler, Paul D.; Koehler, Jodi L.; Coles, James, Jr.] Medtronic Inc, Minneapolis, MN USA. [Glotzer, Taya V.] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Daoud, Emile G.] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ezekowitz, Michael D.] Lankenau Inst Med Res, Philadelphia, PA USA. [Hoyt, Robert H.] Iowa Heart Ctr, Des Moines, IA USA. [Wyse, D. George] Libin Cardiovasc Inst Alberta, Calgary, AB, Canada. RP Ziegler, PD (reprint author), Medtronic Inc, Minneapolis, MN USA. EM paul.david.ziegler@medtronic.com FU Medtronic, Inc. (Minneapolis, Minnesota) FX This study was funded by Medtronic, Inc. (Minneapolis, Minnesota). NR 24 TC 57 Z9 57 U1 0 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV PY 2012 VL 110 IS 9 BP 1309 EP 1314 DI 10.1016/j.amjcard.2012.06.034 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 036CG UT WOS:000311003400017 PM 22819433 ER PT J AU Munoz, R Carmody, JS Stylopoulos, N Davis, P Kaplan, LM AF Munoz, Rodrigo Carmody, Jill S. Stylopoulos, Nicholas Davis, Philip Kaplan, Lee M. TI Isolated duodenal exclusion increases energy expenditure and improves glucose homeostasis in diet-induced obese rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE diabetes; bariatric surgery; energy balance; medical devices ID Y GASTRIC BYPASS; TYPE-2 DIABETES-MELLITUS; WEIGHT-LOSS; BARIATRIC SURGERY; BILE-ACIDS; CALORIE RESTRICTION; SLEEVE GASTRECTOMY; MEDICAL THERAPY; INCRETIN LEVELS; JEJUNAL BYPASS AB Munoz R, Carmody JS, Stylopoulos N, Davis P, Kaplan LM. Isolated duodenal exclusion increases energy expenditure and improves glucose homeostasis in diet-induced obese rats. Am J Physiol Regul Integr Comp Physiol 303: R985-R993, 2012. First published September 12, 2012; doi:10.1152/ajpregu.00262.2012.-Roux-en-Y gastric bypass (RYGB) in rodent models reduces food intake (FI), increases resting energy expenditure (EE), and improves glycemic control. We have shown that mimicking the duodenal component of RYGB by implantation of a 10-cm endoluminal sleeve device (ELS-10) induces weight loss and improves glycemic control in diet-induced obese (DIO) rats. We sought to determine the mechanisms and structural requirements of these effects. We examined the effects of ELS-10 devices implanted in male DIO rats on body weight, food intake (FI), meal patterns, total and resting EE, and multiple parameters of glucose homeostasis, comparing them with sham-operated (SO) rats and with SO rats weight matched to the ELS-10-treated group. To determine the extent of duodenal exclusion required to influence metabolic outcomes, we compared the effects of implanting 10-, 4-, or 1-cm ELS devices. ELS-10 rats exhibited 13% higher total and 9% higher resting EE than SO controls. ELS-10 rats also exhibited enhanced postprandial GLP-1 secretion and improved glucose tolerance and insulin sensitivity out of proportion to the effects of weight loss alone. Implantation of 4- or 1-cm ELS devices had no effect on EE and limited effects on glucose homeostasis. Complete duodenal exclusion with ELS-10 induces weight loss by decreasing FI and increasing EE and improves glycemic control through weight loss-independent mechanisms. Thus signals originating in the proximal small intestine appear to exert a direct influence on the physiological regulation of EE and glucose homeostasis. Their selective manipulation could provide effective new therapies for obesity and diabetes that mimic the benefits of RYGB. C1 [Munoz, Rodrigo; Carmody, Jill S.; Stylopoulos, Nicholas; Davis, Philip; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02129 USA. [Munoz, Rodrigo; Carmody, Jill S.; Stylopoulos, Nicholas; Davis, Philip; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. [Munoz, Rodrigo; Carmody, Jill S.; Stylopoulos, Nicholas; Davis, Philip; Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA USA. [Munoz, Rodrigo] Pontificia Univ Catolica Chile, Fac Med, Dept Cirugia Digest, Santiago, Chile. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Obes Metab & Nutr Inst, 149 13th St,Rm 8219, Boston, MA 02129 USA. EM LMKaplan@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-088661, DK-026400]; GI Dynamics FX This work was supported by grants DK-088661 and DK-026400 from the National Institute of Diabetes and Digestive and Kidney Diseases. This study was supported in part by a research grant from GI Dynamics to L. M. Kaplan. NR 44 TC 13 Z9 13 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2012 VL 303 IS 10 BP R985 EP R993 DI 10.1152/ajpregu.00262.2012 PG 9 WC Physiology SC Physiology GA 039DW UT WOS:000311225000001 PM 22972837 ER PT J AU Liu, Y Rajagopal, M Lee, K Battini, L Flores, D Gusella, GL Pao, AC Rohatgi, R AF Liu, Yu Rajagopal, Madhumitha Lee, Kim Battini, Lorenzo Flores, Daniel Gusella, G. Luca Pao, Alan C. Rohatgi, Rajeev TI Prostaglandin E-2 mediates proliferation and chloride secretion in ADPKD cystic renal epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE prostanoid; secretory renal epithelia; cystic epithelia; cyclooxygenase ID POLYCYSTIC KIDNEY-DISEASE; COLLECTING DUCT CELLS; RETINAL-PIGMENT EPITHELIUM; REGULATED KINASE PATHWAY; COLORECTAL-CANCER; COLON-CANCER; PROSTANOID PRODUCTION; EP2 RECEPTOR; GROWTH; EXPRESSION AB Liu Y, Rajagopal M, Lee K, Battini L, Flores D, Gusella GL, Pao AC, Rohatgi R. Prostaglandin E-2 mediates proliferation and chloride secretion in ADPKD cystic renal epithelia. Am J Physiol Renal Physiol 303: F1425-F1434, 2012. First published August 29, 2012; doi: 10.1152/ajprenal.00010.2012.-Prostaglandin E-2 (PGE(2)) contributes to cystogenesis in genetically nonorthologous models of autosomal dominant polycystic kidney disease (ADPKD). However, it remains unknown whether PGE(2) induces the classic features of cystic epithelia in genetically orthologous models of ADPKD. We hypothesized that, in ADPKD epithelia, PGE(2) induces proliferation and chloride (Cl-) secretion, two archetypal phenotypic features of ADPKD. To test this hypothesis, proliferation and Cl- secretion were measured in renal epithelial cells deficient in polycystin-1 (PC-1). PC-1-deficient cells increased in cell number (proliferated) faster than PC-1-replete cells, and this proliferative advantage was abrogated by cyclooxygenase inhibition, indicating a role for PGE(2) in cell proliferation. Exogenous administration of PGE(2) increased proliferation of PC-1-deficient cells by 38.8 +/- 5.2% (P < 0.05) but inhibited the growth of PC-1-replete control cells by 49.4 +/- 1.9% (P < 0.05). Next, we tested whether PGE(2)-specific E prostanoid (EP) receptor agonists induce intracellular cAMP and downstream beta-catenin activation. PGE(2) and EP4 receptor agonism (TCS 2510) increased intracellular cAMP concentration and the abundance of active beta-catenin in PC-1-deficient cells, suggesting a mechanism for PGE(2)-mediated proliferation. Consistent with this hypothesis, antagonizing EP4 receptors reverted the growth advantage of PC-1-deficient cells, implicating a central role for the EP4 receptor in proliferation. To test whether PGE(2)-dependent Cl- secretion is also enhanced in PC-1-deficient cells, we used an Ussing chamber to measure short-circuit current (I-sc). Addition of PGE(2) induced a fivefold higher increase in I-sc in PC-1-deficient cells compared with PC-1-replete cells. This PGE(2)-induced increase in I-sc in PC-1-deficient cells was blocked by CFTR-172 and flufenamic acid, indicating that PGE(2) activates CFTR and calcium-activated Cl channels. In conclusion, PGE(2) activates aberrant signaling pathways in PC-1-deficient epithelia that contribute to the proliferative and secretory phenotype characteristic of ADPKD and suggests a therapeutic role for PGE(2) inhibition and EP4 receptor antagonism. C1 [Liu, Yu; Lee, Kim; Battini, Lorenzo; Flores, Daniel; Gusella, G. Luca; Rohatgi, Rajeev] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Liu, Yu; Flores, Daniel; Rohatgi, Rajeev] James J Peters Vet Affairs Med Ctr, Dept Med, Bronx, NY USA. [Rajagopal, Madhumitha; Pao, Alan C.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Rohatgi, Rajeev] Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. RP Rohatgi, R (reprint author), Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM rajeev.rohatgi@mssm.edu FU Hepato/Renal Fibrocystic Diseases Core Center [P30DK074038]; Department of Veterans Affairs Merit Review [1I01BX000388]; Satellite Healthcare Norman S. Coplon Extramural Grants; National Institutes of Health [5R01DK78231-2]; Department of Defense [W81XWH-09-1-0269] FX This work was supported by Pilot and Feasibility Grant (to R. Rohatgi) from the Hepato/Renal Fibrocystic Diseases Core Center (P30DK074038), Department of Veterans Affairs Merit Review 1I01BX000388 (to R. Rohatgi), Satellite Healthcare Norman S. Coplon Extramural Grants (to A. C. Pao and R. Rohatgi), National Institutes of Health Grant 5R01DK78231-2 and the Department of Defense Grant W81XWH-09-1-0269 to G. L. Gusella. NR 48 TC 14 Z9 14 U1 0 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2012 VL 303 IS 10 BP F1425 EP F1434 DI 10.1152/ajprenal.00010.2012 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 038XU UT WOS:000311208200004 PM 22933297 ER PT J AU Camargo, CA Tsai, CL Sullivan, AF Cleary, PD Gordon, JA Guadagnoli, E Kaushal, R Magid, DJ Rao, SR Blumenthal, D AF Camargo, Carlos A., Jr. Tsai, Chu-Lin Sullivan, Ashley F. Cleary, Paul D. Gordon, James A. Guadagnoli, Edward Kaushal, Rainu Magid, David J. Rao, Sowmya R. Blumenthal, David TI Safety Climate and Medical Errors in 62 US Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID ADVERSE DRUG EVENTS; ACUTE MYOCARDIAL-INFARCTION; QUALITY-OF-CARE; PATIENT SAFETY; HOSPITALIZED-PATIENTS; PERFORMANCE; MODELS; COLORADO; UTAH AB Study objective: We describe the incidence and types of medical errors in emergency departments (EDs) and assess the validity of a survey instrument that identifies systems factors contributing to errors in EDs. Methods: We conducted the National Emergency Department Safety Study in 62 urban EDs across 20 US states. We reviewed 9,821 medical records of ED patients with one of 3 conditions (myocardial infarction, asthma exacerbation, and joint dislocation) to evaluate medical errors. We also obtained surveys from 3,562 staff randomly selected from each ED; survey data were used to calculate average safety climate scores for each ED. Results: We identified 402 adverse events (incidence rate 4.1 per 100 patient visits; 95% confidence interval [CI] 3.7 to 4.5) and 532 near misses (incidence rate 5.4 per 100 patient visits; 95% Cl 5.0 to 5.9). We judged 37% of the adverse events, and all of the near misses, to be preventable (errors); 33% of the near misses were intercepted. In multivariable models, better ED safety climate was not associated with fewer preventable adverse events (incidence rate ratio per 0.2-point increase in ED safety score 0.82; 95% CI 0.57 to 1.16) but was associated with more intercepted near misses (incidence rate ratio 1.79; 95% CI 1.06 to 3.03). We found no association between safety climate and violations of national treatment guidelines. Conclusion: Among the 3 ED conditions studied, medical errors are relatively common, and one third of adverse events are preventable. Improved ED safety climate may increase the likelihood that near misses are intercepted. [Ann Emerg Med. 2012;60:555-563.] C1 [Camargo, Carlos A., Jr.; Tsai, Chu-Lin; Sullivan, Ashley F.; Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.; Gordon, James A.; Blumenthal, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mongan Inst Hlth Policy, Boston, MA USA. [Rao, Sowmya R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Ctr, Boston, MA USA. [Cleary, Paul D.] Yale Univ, Sch Med, Sch Publ Hlth, New Haven, CT USA. [Guadagnoli, Edward] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Kaushal, Rainu] New York Presbyterian Hosp, New York, NY USA. [Kaushal, Rainu] Weill Cornell Med Coll, New York, NY USA. [Magid, David J.] Kaiser Permanente Colorado, Inst Hlth Res, Aurora, CO USA. [Magid, David J.] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Magid, David J.] Univ Colorado, Dept Prevent Med & Biometr, Aurora, CO USA. [Blumenthal, David] US Dept HHS, Off Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. EM ccamargo@partners.org OI TSAI, CHU-LIN/0000-0003-4639-1513 FU Agency for Healthcare Research and Quality (Rockville, MD) [R01 HS013099] FX By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist. This study was supported by grant R01 HS013099 from the Agency for Healthcare Research and Quality (Rockville, MD). NR 51 TC 10 Z9 10 U1 2 U2 17 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2012 VL 60 IS 5 BP 555 EP 563 DI 10.1016/j.annemergmed.2012.02.018 PG 9 WC Emergency Medicine SC Emergency Medicine GA 035FN UT WOS:000310928800004 PM 23089089 ER PT J AU Wen, LS AF Wen, Leana S. TI Another Day, Another Code, Another Thank You SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. EM wen.leana@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2012 VL 60 IS 5 BP 665 EP 665 DI 10.1016/j.annemergmed.2012.07.002 PG 1 WC Emergency Medicine SC Emergency Medicine GA 035FN UT WOS:000310928800021 PM 23089092 ER PT J AU Fisher, J Wald, DA Orr, N Butler, A Morales, A Franzen, D Heitz, C Hiller, K Loftipour, S Senecal, E AF Fisher, J. Wald, D. A. Orr, N. Butler, A. Morales, A. Franzen, D. Heitz, C. Hiller, K. Loftipour, S. Senecal, E. TI National Board of Medical Examiners' Development of an Advanced Clinical Examination in Emergency Medicine SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Academic Assembly of the Council-of-Emergency-Medicine-Residency-Directors (CORD) CY APR 01-14, 2012 CL Atlanta, GA SP Council Emergency Med Residency Directors (CORD) C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. Natl Board Med Examiners, Philadelphia, PA USA. Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. Virginia Tech, Caril Clin, Caril Sch Med, Roanoke, VA USA. Univ Arizona, Arizona Emergency Med Res Ctr, Tucson, AZ USA. Univ Calif Irvine, Irvine, CA USA. Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2012 VL 60 IS 5 MA 81 BP S190 EP S191 PG 2 WC Emergency Medicine SC Emergency Medicine GA 035FN UT WOS:000310928800111 ER PT J AU Madan, JC Salari, RC Saxena, D Davidson, L O'Toole, GA Moore, JH Sogin, ML Foster, JA Edwards, WH Palumbo, P Hibberd, PL AF Madan, Juliette C. Salari, Richard Cowper Saxena, Deepti Davidson, Lisa O'Toole, George A. Moore, Jason H. Sogin, Mitchell L. Foster, James A. Edwards, William H. Palumbo, Paul Hibberd, Patricia L. TI Gut microbial colonisation in premature neonates predicts neonatal sepsis SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID CHRONIC INFLAMMATORY DISORDERS; EMPIRICAL ANTIBIOTIC-TREATMENT; 99TH DAHLEM CONFERENCE; BIRTH-WEIGHT INFANTS; INTENSIVE-CARE-UNIT; INTESTINAL MICROBIOTA; NECROTIZING ENTEROCOLITIS; PRETERM INFANTS; ONSET SEPSIS; INFECTION AB Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality. Understanding microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome. Methods Prospective longitudinal study of premature infants. Stool samples were obtained weekly. DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing, comparing subjects with and without sepsis. Results Six neonates were 24-27 weeks gestation at birth and had 18 samples analysed. Two subjects had no sepsis during the study period, two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation. 324 350 sequences were obtained. The meconium was not sterile and had predominance of Lactobacillus, Staphylococcus and Enterobacteriales. Overall, infants who developed sepsis began life with low microbial diversity, and acquired a predominance of Staphylococcus, while healthy infants had more diversity and predominance of Clostridium, Klebsiella and Veillonella. Conclusions In very low birth weight infants, the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis. Empiric, prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis, but the predominant pathogen previously identified in the microbiome. Our data suggest that there may be a 'healthy microbiome' present in extremely premature neonates that may ameliorate risk of sepsis. More research is needed to determine whether altered antibiotics, probiotics or other novel therapies can re-establish a healthy microbiome in neonates. C1 [Madan, Juliette C.; Edwards, William H.] Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03753 USA. [Salari, Richard Cowper; Moore, Jason H.] Dartmouth Med Sch, Lebanon, NH USA. [Saxena, Deepti; Palumbo, Paul] Dartmouth Hitchcock Med Ctr, Dept Med, Div Infect Dis & Int Hlth, Lebanon, NH 03753 USA. [Davidson, Lisa] Tufts Med Ctr, Boston, MA USA. [O'Toole, George A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Microbiol & Immunol, Hanover, NH 03756 USA. [Sogin, Mitchell L.] Josephine Bay Paul Ctr, Marine Biol Lab, Woods Hole, MA USA. [Foster, James A.] Univ Idaho, Dept Biol Sci & Initiat Bioinformat & Evolutionar, Moscow, ID 83843 USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Dept Pediat, Div Global Hlth, Boston, MA 02114 USA. RP Madan, JC (reprint author), Dartmouth Hitchcock Med Ctr, Dept Pediat, 1 Med Ctr Dr, Lebanon, NH 03753 USA. EM juliette.c.madan@hitchcock.org OI Foster, James/0000-0002-6770-6521 FU Hearst Foundation; Synergy Grant (Dartmouth); Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth); Department of Pediatrics, Dartmouth; Cystic Fibrosis Foundation [STANTO07R0]; NIH [R01 AI59694, P20RR16448, P20RR016454]; NSF [DBI0939454] FX The Hearst Foundation, The Synergy Grant (Dartmouth), The Joshua Burnett Career Development Award through the Hitchcock Foundation (Dartmouth), the Department of Pediatrics, Dartmouth. This work was also supported by a pilot grant from the Cystic Fibrosis Foundation Research Development Program (STANTO07R0). RCS and JHM were funded by NIH R01 AI59694. JAF was funded in part by NIH grants P20RR16448 and P20RR016454 and by NSF DBI0939454. NR 45 TC 78 Z9 83 U1 0 U2 40 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD NOV PY 2012 VL 97 IS 6 BP F456 EP F462 DI 10.1136/archdischild-2011-301373 PG 7 WC Pediatrics SC Pediatrics GA 036JS UT WOS:000311022800013 PM 22562869 ER PT J AU Beksac, M Preffer, F AF Beksac, M. Preffer, F. TI Is it time to revisit our current hematopoietic progenitor cell quantification methods in the clinic? SO BONE MARROW TRANSPLANTATION LA English DT Review DE hematopoietic SCT; CD34; CD133; aldehyde dehydrogenase; flow cytometry ID ALDEHYDE DEHYDROGENASE-ACTIVITY; COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD PROGENITOR; MESENCHYMAL STROMAL CELLS; HUMAN BONE-MARROW; STEM-CELLS; FUNCTIONAL-CHARACTERIZATION; MESSENGER-RNA; CD34(+) CELLS; TRANSPLANTATION AB In the clinical practice of hematopoietic SCT, the minimum numbers of cells required for a successful engraftment are defined on the basis of their CD45 and CD34 expression profiles. However, the quantity of earlier progenitors or CD34-positive cells at different differentiation stages within stem cell grafts is not generally taken into consideration. During the last decade, various teams have quantified the number of cells expressing various combinations of CD34, CD38, CD133, CD90 co-expression and/or aldehyde dehydrogenase functional capacity using flow cytometry. Some of these studies resulted in the greater appreciation that combinations of these Ags were associated with varied myeloid, erythroid and platelet engraftment rates whereas others showed that the relative absence or presence of these markers could define cells responsible for either short-or long-term engraftment. These findings were also extended to differences between progenitor cell populations found within BM vs peripheral or cord-blood grafts. Cells harvested from donors are also generally frozen and stored; thawed cells have variable levels of viability and functional capacity based on the time tested post thaw, which also can be assessed by flow cytometry. Finally, flow cytometry has the potential for analysis of cells carrying a mesenchymal stem cell phenotype, which may be quiescent within some of the stem cell products. This review will address the need for stem cell subpopulation quantification and summarize existing published data to identify some Ags and functional characteristics that can be applicable to daily clinical practice. Bone Marrow Transplantation (2012) 47, 1391-1396; doi:10.1038/bmt.2011.240; published online 5 December 2011 C1 [Beksac, M.] Ankara Univ, Sch Med, Dept Hematol, TR-06620 Ankara, Turkey. [Preffer, F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Beksac, M (reprint author), Ankara Univ, Sch Med, Dept Hematol, Cebeci Yerleskesi, TR-06620 Ankara, Turkey. EM beksac@medicine.ankara.edu.tr RI Beksac, Meral/D-6411-2013 NR 57 TC 5 Z9 5 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2012 VL 47 IS 11 BP 1391 EP 1396 DI 10.1038/bmt.2011.240 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 033KS UT WOS:000310795500002 PM 22139068 ER PT J AU Siddiquee, Z Zane, NA Smith, RN Stone, JR AF Siddiquee, Zakir Zane, Nicholas A. Smith, R. Neal Stone, James R. TI Dense IgG4 plasma cell infiltrates associated with chronic infectious aortitis: implications for the diagnosis of IgG4-related disease SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE Aortitis; IgG4-related disease; IgG4; Staphylococcus aureus; Infection; Diagnostic criteria ID SYSTEMIC-DISEASE; LYMPHOPLASMACYTIC AORTITIS; SURGICAL PATHOLOGY; PERIAORTITIS AB Background: IgG4-related aortitis is a newly recognized form of noninfectious aortitis that occurs as part of the spectrum of a systemic disease referred to as IgG4-related disease. IgG4-related aortitis is distinguished from giant cell aortitis and Takayasu aortitis in part by the presence of increased numbers of IgG4-expressing plasma cells. Chronic infectious aortitis can also display lymphoplasmacytic infiltrates, but the degree of IgG4 expression in these cases has not been specifically evaluated. Methods: Two cases of chronic active infectious abdominal aortitis were prospectively identified. Both were due to gram-positive bacteria, and at least one of the cases was due to chronic active Staphylococcus aureus infection. The degree of IgG4 plasma cell infiltration was assessed by immunohistochemistry. Results: Both cases of chronic infectious aortitis focally displayed high levels of IgG4-expressing plasma cells, greater than 50% of the IgG-expressing plasma cells, and greater than 50 IgG4-expressing plasma cells per high-power field. Conclusions: Focal dense IgG4 plasma cell infiltrates can be seen in association with chronic infectious aortitis due to gram-positive bacteria, including Staphylococcus aureus. This observation supports the proposal that chronic Staphylococcus aureus infection may stimulate a Th2-mediated elevation in IgG4. The pathologic diagnosis of IgG4-related aortitis should not be based solely on the presence of increased IgG4 plasma cell counts from immunohistochemistry, but requires consideration of the overall pathology, including careful exclusion of infectious aortitis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Siddiquee, Zakir; Zane, Nicholas A.; Smith, R. Neal; Stone, James R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Simches Res Bldg,Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU Massachusetts General Hospital FX This work was supported by Massachusetts General Hospital. NR 18 TC 17 Z9 17 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD NOV-DEC PY 2012 VL 21 IS 6 BP 470 EP 475 DI 10.1016/j.carpath.2012.02.001 PG 6 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 036YK UT WOS:000311068000004 PM 22406174 ER PT J AU Laserna, E Sibila, O Aguilar, PR Mortensen, EM Anzueto, A Blanquer, JM Sanz, F Rello, J Marcos, PJ Velez, MI Aziz, N Restrepo, MI AF Laserna, Elena Sibila, Oriol Aguilar, Patrick R. Mortensen, Eric M. Anzueto, Antonio Blanquer, Jose M. Sanz, Francisco Rello, Jordi Marcos, Pedro J. Velez, Maria I. Aziz, Nivin Restrepo, Marcos I. TI Hypocapnia and Hypercapnia Are Predictors for ICU Admission and Mortality in Hospitalized Patients With Community-Acquired Pneumonia SO CHEST LA English DT Article ID RESEARCH TEAM COHORT; INTENSIVE-CARE-UNIT; CARBON-DIOXIDE; VALIDATION; GUIDELINES; SEVERITY; OUTCOMES; MANAGEMENT; DATABASE; THERAPY AB Objective: The purpose of our study was to examine in patients hospitalized with community-acquired pneumonia (CAP) the association between abnormal PaCO2 and ICU admission and 30-day mortality. Methods: A retrospective cohort study was conducted at two tertiary teaching hospitals. Eligible subjects were admitted with a diagnosis of CAR Arterial blood gas analyses were obtained with measurement of PaCO2 on admission. Multivariate analyses were performed using 30-day mortality and ICU admission as the dependent measures. Results: Data were abstracted on 453 subjects with a documented arterial blood gas analysis. One hundred eighty-nine patients (41%) had normal PaCO2 (35-45 mm Hg), 194 patients (42%) had a PaCO2 <35 mm Hg (hypocapnic), and 70 patients (15%) had a PaCO2 > 45 mm Hg (hypercapnic). In the multivariate analysis, after adjusting for severity of illness, hypocapnic patients had greater 30-day mortality (OR = 2.84; 95% CI, 1.28-6.30) and a higher need for ICU admission (OR = 2.88; 95% CI, 1.68-4.95) compared with patients with normal PaCO2. In addition, hypercapnic patients had a greater 30-day mortality (OR = 3.38; 95% CI, 1.38-8.30) and a higher need for ICU admission (OR = 5.35; 95% CI, 2.80-10.23). When patients with COPD were excluded from the analysis, the differences persisted between groups. Conclusion: In hospitalized patients with CAP, both hypocapnia and hypercapnia were associated with an increased need for ICU admission and higher 30-day mortality. These findings persisted after excluding patients with CAP and with COPD. Therefore, PaCO2 should be considered for inclusion in future severity stratification criteria to appropriate identified patients who will require a higher level of care and are at risk for increased mortality. CHEST 2012; 142(5):1193-1199 C1 [Laserna, Elena; Sibila, Oriol; Aguilar, Patrick R.; Anzueto, Antonio; Velez, Maria I.; Aziz, Nivin; Restrepo, Marcos I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Laserna, Elena] Hosp Comarcal Mollet, Serv Pneumol, Mollet Del Valles, Spain. [Sibila, Oriol] Hosp Santa Creui & St Pau, Serv Pneumol, Barcelona, Spain. [Mortensen, Eric M.] VA N Texas Hlth Care Syst, Dallas, TX USA. [Mortensen, Eric M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Anzueto, Antonio; Velez, Maria I.; Restrepo, Marcos I.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Blanquer, Jose M.] Unidad Cuidados Intens Resp Hosp Clin Univ, Valencia, Spain. [Sanz, Francisco] Consorci Hosp Gen Univ, Serv Neumol, Valencia, Spain. [Rello, Jordi] Univ Autonoma Barcelona, Serv Med Intens, Hosp Vall dHebron, CIBERES,VHICU, E-08193 Barcelona, Spain. [Marcos, Pedro J.] Complejo Hosp Univ A Coruna, Serv Neumol, La Coruna, Spain. Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. RP Restrepo, MI (reprint author), S Texas Vet Hlth Care Syst ALMD, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014; Marcos, Pedro J/K-9965-2015; OI Marcos, Pedro J/0000-0001-9600-3537; Rello, Jordi/0000-0003-0676-6210; Mortensen, Eric/0000-0002-3880-5563 FU Howard Hughes Medical Institute faculty start-up grant [00378-001]; Department of Veteran Affairs Veterans Integrated Service Network [17]; Sociedad Espanola de Neumologia y Cirugia Toracica; Societat Catalana de Pneumologia; Fundacio Catalana de Pneumologia; Instituto de Salud Carlos III [BAE11/00102]; National Heart, Lung, and Blood Institute [K23HL096054] FX This research was supported by a Howard Hughes Medical Institute faculty start-up grant [00378-001] and a Department of Veteran Affairs Veterans Integrated Service Network 17 new faculty grant. Drs Laserna and Sibila are supported by Sociedad Espanola de Neumologia y Cirugia Toracica, Societat Catalana de Pneumologia, and Fundacio Catalana de Pneumologia. Dr Sibila is supported by Instituto de Salud Carlos III [Grant BAE11/00102]. Dr Restrepo's time is partially protected by an award from the National Heart, Lung, and Blood Institute [K23HL096054]. NR 33 TC 16 Z9 16 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2012 VL 142 IS 5 BP 1193 EP 1199 DI 10.1378/chest.12-0576 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 036EV UT WOS:000311010100022 PM 22677348 ER PT J AU Maguen, S Metzler, TJ Bosch, J Marmar, CR Knight, SJ Neylan, TC AF Maguen, Shira Metzler, Thomas J. Bosch, Jeane Marmar, Charles R. Knight, Sara J. Neylan, Thomas C. TI KILLING IN COMBAT MAY BE INDEPENDENTLY ASSOCIATED WITH SUICIDAL IDEATION SO DEPRESSION AND ANXIETY LA English DT Article DE suicide; killing; depression; stress disorders; posttraumatic; war; veterans ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH SYMPTOMS; VIETNAM VETERANS; WAR VETERANS; TRAUMATIC STRESS; US VETERANS; RISK; IMPACT; IRAQ; PREVALENCE AB Background The United States military has lost more troops to suicide than to combat for the second year in a row and better understanding combat-related risk factors for suicide is critical. We examined the association of killing and suicide among war veterans after accounting for PTSD, depression, and substance use disorders. Methods We utilized a cross-sectional, retrospective, nationally representative sample of Vietnam veterans from the National Vietnam Veterans Readjustment Study (NVVRS). In order to perform a more in depth analysis, we utilized a subsample of these data, the NVVRS Clinical Interview Sample (CIS), which is representative of 1.3 million veterans who were eligible for the clinical interview by virtue of living in proximity to an interview site, located within 28 standard metropolitan regions throughout the United States. Results Veterans who had higher killing experiences had twice the odds of suicidal ideation, compared to those with lower or no killing experiences (OR = 1.99, 95% CI = 1.073.67), even after adjusting for demographic variables, PTSD, depression, substance use disorders, and adjusted combat exposure. PTSD (OR = 3.42, 95% CI = 1.0910.73), depression (OR = 11.49, 95% CI = 2.1262.38), and substance use disorders (OR = 3.98, 95% CI = 1.0115.60) were each associated with higher odds of suicidal ideation. Endorsement of suicide attempts was most strongly associated with PTSD (OR = 5.52, 95% CI = 1.2125.29). Conclusions Killing experiences are not routinely examined when assessing suicide risk. Our findings have important implications for conducting suicide risk assessments in veterans of war. Depression and Anxiety 00:16, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Maguen, Shira] San Francisco VA Med Ctr, PTSD Program 116 P, San Francisco, CA 94121 USA. [Maguen, Shira; Metzler, Thomas J.; Knight, Sara J.; Neylan, Thomas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Marmar, Charles R.] NYU, Langone Med Ctr, New York, NY USA. RP Maguen, S (reprint author), San Francisco VA Med Ctr, PTSD Program 116 P, 4150 Clement St, San Francisco, CA 94121 USA. EM Shira.Maguen@va.gov FU VA Health Services Research and Development Career Development Award [RCD 06-042] FX This research was supported by the VA Health Services Research and Development Career Development Award (RCD 06-042: Maguen). NR 36 TC 34 Z9 34 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2012 VL 29 IS 11 BP 918 EP 923 DI 10.1002/da.21954 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 031YS UT WOS:000310679300002 PM 22505038 ER PT J AU Hoge, EA Lawson, EA Metcalf, CA Keshaviah, A Zak, PJ Pollack, MH Simon, NM AF Hoge, Elizabeth A. Lawson, Elizabeth A. Metcalf, Christina A. Keshaviah, Aparna Zak, Paul J. Pollack, Mark H. Simon, Naomi M. TI PLASMA OXYTOCIN IMMUNOREACTIVE PRODUCTS AND RESPONSE TO TRUST IN PATIENTS WITH SOCIAL ANXIETY DISORDER SO DEPRESSION AND ANXIETY LA English DT Article DE social anxiety disorder; oxytocin; trust; neuropeptide ID CEREBROSPINAL-FLUID; BLOOD-PRESSURE; SCHIZOPHRENIC-PATIENTS; BEHAVIOR; GAME; VASOPRESSIN; CORTISOL; SUPPORT; STRESS; HUMANS AB Background: Generalized Social Anxiety Disorder (GSAD) is characterized by excessive fear and avoidance of several types of social and performance situations. The pathophysiology is not well understood, but research in animals and humans has provided evidence that oxytocin helps regulate normal social affiliative behavior. Previous work in healthy male subjects demonstrated a rise in plasma oxytocin after receiving a high trust signal. To examine the oxytocin system in GSAD, we measured plasma oxytocin in GSAD patients and controls, before and after the social "Trust Game," a neuroeconomic test examining trust behavior and reaction to trust using real monetary incentives. Methods: Thirty-nine subjects with GSAD and 28 healthy controls provided three blood samples for oxytocin measurement before the Trust Game, and one sample after the game. Plasma estradiol was also measured at baseline. The Trust Game protocol version prioritized the sending of a signal of high cooperation and trust to all participants. All analyses controlled for gender and estradiol levels. Results: Mean oxytocin levels post-Trust Game (P = .025), and overall (area under the curve, P = .011) were lower in GSAD patients compared to controls, after controlling for sex and estradiol. There was no significant change in oxytocin levels after the game in either group. Conclusions: We report low plasma oxytocin levels in patients with GSAD during a prosocial laboratory task paradigm. Additional research will be important to further examine the relationship between oxytocin and social behavior in GSAD. Depression and Anxiety 29:924-930, 12012. (c) 2012 Wiley Periodicals, Inc. C1 [Hoge, Elizabeth A.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, Boston, MA 02114 USA. [Hoge, Elizabeth A.; Lawson, Elizabeth A.; Metcalf, Christina A.; Keshaviah, Aparna; Simon, Naomi M.] Harvard Univ, Sch Med, Boston, MA USA. [Lawson, Elizabeth A.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Zak, Paul J.] Claremont Grad Univ, Ctr Neuroecon Studies, Claremont, CA USA. [Pollack, Mark H.] Rush Univ, Ctr Med, Dept Psychiat, Chicago, IL 60612 USA. RP Hoge, EA (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Dept Psychiat, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ehoge@partners.org RI Hoge, Elizabeth/H-5879-2012 OI Hoge, Elizabeth/0000-0002-5513-2292 FU Harvard-MIT Health Sciences and Technology/Beth Israel Deaconess Medical Center; Pfizer Inc.; MerckMerck and Company, Inc.; Eli Lilly, Inc; John Templeton Foundation; Harvard Catalyst: The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; Harvard University; Bristol Myers Squibb; Euthymics; Forest Laboratories; GlaxoSmithKline; Eli Lilly; Sepracor; American Foundation for Suicide Prevention; NARSAD; Lilly; Pfizer FX Research Support: Clinical Investigator Training Program: Harvard-MIT Health Sciences and Technology/Beth Israel Deaconess Medical Center, in collaboration with Pfizer Inc. and Merck and Company, Inc.; and Eli Lilly, Inc (EH); also from the John Templeton Foundation (PZ); and from Harvard Catalyst: The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care centers). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health.; Mark Pollack, MD: Grant Funding: Bristol Myers Squibb, Euthymics, Forest Laboratories, GlaxoSmithKline, Eli Lilly, Sepracor. Consulting/honorarium: Brain Cells, Eli Lilly, Johnson and Johnson, Meda-vante, Labopharm, Mindsite, Otsuka, Sepracor, Targia Pharmaceuticals, Pfizer. CME supported activities: Astra-Zeneca, Sepracor, Pfizer. Equity: Medavante, Mensante Corporation, Mindsite, Targia Pharmaceuticals. Royalty/patent: SIGH-A, SAFER interviews; Naomi Simon, MD: Grants: American Foundation for Suicide Prevention, Forest Laboratories, NARSAD, Glaxo SmithKline, Lilly, Pfizer, Sepracor. Payment for lectures: Pfizer NR 51 TC 14 Z9 16 U1 4 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD NOV PY 2012 VL 29 IS 11 BP 924 EP 930 DI 10.1002/da.21973 PG 7 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 031YS UT WOS:000310679300003 PM 22807189 ER PT J AU Chuengsamarn, S Rattanamongkolgul, S Luechapudiporn, R Phisalaphong, C Jirawatnotai, S AF Chuengsamarn, Somlak Rattanamongkolgul, Suthee Luechapudiporn, Rataya Phisalaphong, Chada Jirawatnotai, Siwanon TI Curcumin Extract for Prevention of Type 2 Diabetes SO DIABETES CARE LA English DT Article ID BETA-CELL FUNCTION; INSULIN-RESISTANCE; EXPERT COMMITTEE; BLOOD-GLUCOSE; KK-A(Y) MICE; LONGA; SUPPLEMENTATION; INFLAMMATION; DIAGNOSIS; METFORMIN AB OBJECTIVE-To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population. RESEARCH DESIGN AND METHODS-This randomized, double-blinded, placebo-controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in beta-cell functions (homeostasis model assessment [HOMA]-beta, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention. RESULTS-After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of beta-cells, with higher HOMA-beta (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group. CONCLUSIONS-A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of beta-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial. C1 [Chuengsamarn, Somlak] Srinakharinwirot Univ, Div Endocrinol & Metab, Fac Med, HRH Princess Maha Chakri Sirindhorn Med Ctr, Nakornnayok, Thailand. [Chuengsamarn, Somlak] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Rattanamongkolgul, Suthee] Srinakharinwirot Univ, Dept Prevent & Social Med, Fac Med, HRH Princess Maha Chakri Sirindhorn Med Ctr, Nakornnayok, Thailand. [Luechapudiporn, Rataya] Chulalongkorn Univ, Fac Pharmaceut Sci, Dept Pharmacol & Physiol, Bangkok, Thailand. [Phisalaphong, Chada] Thai Govt Pharmaceut Org, Res & Dev Inst, Bangkok, Thailand. [Jirawatnotai, Siwanon] Mahidol Univ, Inst Mol Biosci, Salaya, Nakhon Pratom, Thailand. [Jirawatnotai, Siwanon] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Chuengsamarn, S (reprint author), Srinakharinwirot Univ, Div Endocrinol & Metab, Fac Med, HRH Princess Maha Chakri Sirindhorn Med Ctr, Nakornnayok, Thailand. EM somlukc@hotmail.com FU Thai TraditionalMedical Knowledge Fund; Department for Development of Thai Traditional and Alternative Medicine, Ministry of Public Health FX This study was supported by a grant from Thai TraditionalMedical Knowledge Fund and the Department for Development of Thai Traditional and Alternative Medicine, Ministry of Public Health (to S.C.). NR 32 TC 90 Z9 96 U1 3 U2 32 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2012 VL 35 IS 11 BP 2121 EP 2127 DI 10.2337/dc12-0116 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 041TM UT WOS:000311424100008 PM 22773702 ER PT J AU Russell, SJ El-Khatib, FH Nathan, DM Magyar, KL Jiang, J Damiano, ER AF Russell, Steven J. El-Khatib, Firas H. Nathan, David M. Magyar, Kendra L. Jiang, John Damiano, Edward R. TI Blood Glucose Control in Type 1 Diabetes With a Bihormonal Bionic Endocrine Pancreas SO DIABETES CARE LA English DT Article ID INSULIN DELIVERY; HYPOGLYCEMIA; COMPLICATIONS; MELLITUS AB OBJECTIVE-To test whether safe and effective glycemic control could be achieved in type 1 diabetes using a bihormonal bionic endocrine pancreas driven by a continuous glucose monitor in experiments lasting more than two days and including six high-carbohydrate meals and exercise as challenges to glycemic control. RESEARCH DESIGN AND METHODS-Six subjects with type 1 diabetes and no endogenous insulin secretion participated in two 51-h experiments. Blood glucose was managed with a bionic endocrine pancreas controlling subcutaneous delivery of insulin and glucagon with insulin pumps. A partial meal-priming bolus of insulin (0.035 units/kg/meal, then 0.05 units/kg/meal in repeat experiments) was administered at the beginning of each meal (on average 78 6 12 g of carbohydrates per meal were consumed). Plasma glucose (PG) control was evaluated with a reference quality measurement on venous blood every 15 min. RESULTS-The overall mean PG was 158 mg/dL, with 68% of PG values in the range of 70180 mg/dL. There were no significant differences in mean PG between larger and smaller meal-priming bolus experiments. Hypoglycemia (PG,70 mg/dL) was rare, with eight incidents during 576 h of closed-loop control (0.7% of total time). During 192 h of nighttime control, mean PG was 123 mg/dL, with 93% of PG values in the range of 70-180 mg/dL and only one episode of mild hypoglycemia (minimum PG 62 mg/dL). CONCLUSIONS-A bihormonal bionic endocrine pancreas achieved excellent glycemic control with minimal hypoglycemia over the course of two days of continuous use despite high-carbohydrate meals and exercise. A trial testing a wearable version of the system under free-living conditions is justified. C1 [El-Khatib, Firas H.; Jiang, John; Damiano, Edward R.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Russell, Steven J.; Nathan, David M.; Magyar, Kendra L.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Russell, Steven J.; Nathan, David M.; Magyar, Kendra L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Russell, Steven J.; Nathan, David M.; Magyar, Kendra L.] Harvard Univ, Sch Med, Boston, MA USA. RP Damiano, ER (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. EM edamiano@bu.edu FU National Institutes of Health [R01-DK-085633]; National Institutes of Health National Center for Research Resources [M01-RR-01066, UL1-RR-025758, 22-2009-798]; Juvenile Diabetes Research Foundation; Charlton Fund for Innovative Research in Diabetes FX Acknowledgments-This study was supported by grant R01-DK-085633 to E.R.D., from the National Institutes of Health; grants M01-RR-01066 and UL1-RR-025758, through the General Clinical Research Center and Clinical and Translational Science Center programs from the National Institutes of Health National Center for Research Resources; Clinical Investigations research grant 22-2009-798 to E.R.D., from the Juvenile Diabetes Research Foundation; and a grant to D.M.N. from the Charlton Fund for Innovative Research in Diabetes. NR 17 TC 77 Z9 77 U1 0 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2012 VL 35 IS 11 BP 2148 EP 2155 DI 10.2337/dc12-0071/-/DC1 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 041TM UT WOS:000311424100012 PM 22923666 ER PT J AU Krolewski, AS Warram, JH Forsblom, C Smiles, AM Thorn, L Skupien, J Harjutsalo, V Stanton, R Eckfeldt, JH Inker, LA Groop, PH AF Krolewski, Andrzej S. Warram, James H. Forsblom, Carol Smiles, Adam M. Thorn, Lena Skupien, Jan Harjutsalo, Valma Stanton, Robert Eckfeldt, John H. Inker, Lesley A. Groop, Per-Henrik TI Serum Concentration of Cystatin C and Risk of End-Stage Renal Disease in Diabetes SO DIABETES CARE LA English DT Article ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; ESTIMATING GFR; CREATININE; ASSOCIATION; EQUATION; VALUES; ESRD; CKD AB OBJECTIVE-Patients with diabetes have a high risk of end-stage renal disease (ESRD). We examined whether prediction of this outcome, according to chronic kidney disease (CKD) staging by creatinine-based estimates of the glomerular filtration rate (eGFRcreat), is improved by further staging with serum cystatin C-based estimates (eGFRcyst). RESEARCH DESIGN AND METHODS-Patients with diabetes in CKD stages 1-3 were selected from three cohorts: two from Joslin Diabetes Center, one with type 1 diabetes (N = 364) and one with type 2 diabetes (N = 402), and the third from the Finnish Diabetic Nephropathy (FinnDiane) Study of type 1 (N = 399). Baseline serum concentrations of creatinine and cystatin C were measured in all patients. Follow-up averaged 8-10 years and onsets of ESRD (n = 246) and death unrelated to ESRD (n = 159) were ascertained. RESULTS-Although CKD staging by eGFRcyst was concordant with that by eGFRcreat for 62% of Joslin patients and 73% of FinnDiane patients, those given a higher stage by eGFRcyst than eGFRcreat had a significantly higher risk of ESRD than those with concordant staging in all three cohorts (hazard ratio 2.3 [95% CI 1.8-3.1]). Similarly, patients at a lower stage by eGFRcyst than by eGFRcreat had a lower risk than those with concordant staging (0.30 [0.13-0.68]). Deaths unrelated to ESRD followed the same pattern, but differences were not as large. CONCLUSIONS-In patients with diabetes, CKD staging based on eGFRcyst significantly improves ESRD risk stratification based on eGFRcreat. This conclusion can be generalized to patients with type 1 and type 2 diabetes and to diabetic patients in the U. S. and Finland. Diabetes Care 35: 2311-2316, 2012 C1 [Krolewski, Andrzej S.; Warram, James H.; Smiles, Adam M.; Skupien, Jan; Stanton, Robert] Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div, Boston, MA 02115 USA. [Krolewski, Andrzej S.; Warram, James H.; Smiles, Adam M.; Skupien, Jan; Stanton, Robert] Harvard Univ, Sch Med, Clin Div, Boston, MA 02115 USA. [Krolewski, Andrzej S.; Skupien, Jan] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Forsblom, Carol; Thorn, Lena; Harjutsalo, Valma; Groop, Per-Henrik] Folkhalsan Res Ctr, Folkhalsan Inst Genet, Helsinki, Finland. [Forsblom, Carol; Thorn, Lena; Groop, Per-Henrik] Univ Helsinki, Cent Hosp, Div Nephrol, Dept Med, Helsinki, Finland. [Stanton, Robert] Harvard Univ, Beth Israel Deaconess Med Ctr, Renal Div, Sch Med, Boston, MA 02215 USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Inker, Lesley A.] Tufts Univ, Sch Med, Div Nephrol, Tufts Med Ctr, Boston, MA 02111 USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Res Div, Boston, MA 02115 USA. EM andrzej.krolewski@joslin.harvard.edu FU Juvenile Diabetes Research Foundation (JDRF) [1-2008-1018]; National Institutes of Health [DK-41526, DK-067638]; JDRF [3-2009-397]; Folkhalsan Research Foundation; Wilhelm and Else Stockmann Foundation; Livoch Halsa Foundation; Finnish Medical Society (Finska Lakaresallskapet); [K23-DK-081017] FX This project was supported through Juvenile Diabetes Research Foundation (JDRF) Research Grant 1-2008-1018 (A.S.K.), National Institutes of Health Grants DK-41526 (A.S.K.), DK-067638 (A.S.K.), JDRF Fellowship Grant 3-2009-397 (J.S.), and K23-DK-081017 (L.A.I.).; The FinnDiane Study was supported by grants from the Folkhalsan Research Foundation, the Wilhelm and Else Stockmann Foundation, the Livoch Halsa Foundation, and the Finnish Medical Society (Finska Lakaresallskapet). NR 20 TC 24 Z9 27 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2012 VL 35 IS 11 BP 2311 EP 2316 DI 10.2337/dc11-2220 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 041TM UT WOS:000311424100036 PM 22851596 ER PT J AU Haas, L Maryniuk, M Beck, J Cox, CE Duker, P Edwards, L Fisher, EB Hanson, L Kent, D Kolb, L McLaughlin, S Orzeck, E Piette, JD Rhinehart, AS Rothman, R Sklaroff, S Tomky, D Youssef, G AF Haas, Linda Maryniuk, Melinda Beck, Joni Cox, Carla E. Duker, Paulina Edwards, Laura Fisher, Edwin B. Hanson, Lenita Kent, Daniel Kolb, Leslie McLaughlin, Sue Orzeck, Eric Piette, John D. Rhinehart, Andrew S. Rothman, Russell Sklaroff, Sara Tomky, Donna Youssef, Gretchen CA 2012 Stand Revision Task Force TI National Standards for Diabetes Self-Management Education and Support SO DIABETES CARE LA English DT Article ID RANDOMIZED-CONTROLLED-TRIAL; CHRONIC CARE MODEL; CHRONIC DISEASE MANAGEMENT; QUALITY-OF-LIFE; AFRICAN-AMERICAN; GLYCEMIC CONTROL; CLINICAL CHARACTERISTICS; MEDICARE BENEFICIARIES; REGISTERED DIETITIANS; COMPLICATIONS TRIAL C1 [Haas, Linda] VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA USA. [Maryniuk, Melinda] Joslin Diabet Ctr, Boston, MA 02215 USA. [Beck, Joni] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Edmond, OK USA. [Cox, Carla E.] Western Montana Clin, Missoula, MT USA. [Duker, Paulina] Amer Diabet Assoc, Diabet Educ Clin Programs, Alexandria, VA USA. [Edwards, Laura] Ctr Healthy N Carolina, Apex, NC USA. [Fisher, Edwin B.] Univ N Carolina, Amer Acad Family Phys Fdn, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Fisher, Edwin B.] Univ N Carolina, Dept Hlth Behav, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Hanson, Lenita] Ultracare Endocrine & Diabet Consultants, Venice, FL USA. [Kent, Daniel] Grp Hlth Cent Specialty Clin, Seattle, WA USA. [Kolb, Leslie] Amer Assoc Diabet Educ, Diabet Educ Accreditat Program, Chicago, IL USA. [McLaughlin, Sue] On Site Hlth & Wellness LLC, Omaha, NE USA. [Orzeck, Eric] Endocrinol Associates, Houston, TX USA. [Piette, John D.] VA Ctr Clin Management Res, Ann Arbor, MI USA. [Piette, John D.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Rhinehart, Andrew S.] Johnston Mem Diabet Care Ctr, Abingdon, VA USA. [Rothman, Russell] Vanderbilt Univ, Med Ctr, Ctr Hlth Serv Res, Nashville, TN USA. [Tomky, Donna] ABQ Hlth Partners, Dept Endocrinol & Diabet, Albuquerque, NM USA. [Youssef, Gretchen] MedStar Diabet Inst MedStar Hlth, Washington, DC USA. RP Haas, L (reprint author), VA Puget Sound Hlth Care Syst Hosp & Specialty Me, Seattle, WA USA. EM linda.haas@va.gov; melinda.maryniuk@joslin.harvard.edu NR 160 TC 42 Z9 43 U1 2 U2 14 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2012 VL 35 IS 11 BP 2393 EP 2401 DI 10.2337/dc12-1707 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 041TM UT WOS:000311424100050 PM 22995096 ER PT J AU Bhattacharya, A Hamilton, R Rios, C Jernigan, AL Zhang, YQ Sabia, M Rahman, MM Li, Y Qi, WB Van Remmen, H AF Bhattacharya, Arunabh Hamilton, Ryan Rios, Carmen Jernigan, Amanda L. Zhang, Yiqiang Sabia, Marian Rahman, Md M. Li, Yan Qi, Wenbo Van Remmen, Holly TI Divergent Roles for 12/15-Lipoxygenase and 5-Lipoxygenase Lipid Metabolic Pathways in Neurogenic Muscle Atrophy SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Bhattacharya, Arunabh; Hamilton, Ryan; Rios, Carmen; Jernigan, Amanda L.; Zhang, Yiqiang; Sabia, Marian; Rahman, Md M.; Li, Yan; Qi, Wenbo; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S124 EP S124 DI 10.1016/j.freeradbiomed.2012.10.306 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600322 ER PT J AU Mashmoushi, AK Hofbauer, AF Gilkeson, GS Oates, JC AF Mashmoushi, Ahmad K. Hofbauer, Ann F. Gilkeson, Gary S. Oates, Jim C. TI Role of Nitric Oxide in Podocyte Physiology in Lupus Nephritis SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Mashmoushi, Ahmad K.; Hofbauer, Ann F.; Gilkeson, Gary S.; Oates, Jim C.] Med Univ S Carolina, Charleston, SC USA. [Gilkeson, Gary S.; Oates, Jim C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S76 EP S77 DI 10.1016/j.freeradbiomed.2012.10.228 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600195 ER PT J AU Nelson, SK Sterling, D Williams, S Lawson, RJ Berry, JD Cudkowicz, ME AF Nelson, Sally K. Sterling, David Williams, Stephen Lawson, Robert J. Berry, James D. Cudkowicz, Merit E. TI ALS Biomarker Discovery Using SOMAscan (TM) Multiplex Proteomic Technology SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Lawson, Robert J.; Berry, James D.; Cudkowicz, Merit E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S69 EP S69 DI 10.1016/j.freeradbiomed.2012.10.209 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600177 ER PT J AU Richardson, A AF Richardson, Arlan TI HOW WELL DOES THE FREE RADICAL THEORY OF AGING STAND UP TO EXPERIMENTAL TESTING? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 19th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine (SFRBM) CY NOV 14-18, 2012 CL San Diego, CA SP Soc Free Rad Biol & Med (SFRBM) C1 [Richardson, Arlan] Univ Texas Hlth Sci Ctr San Antonio, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2012 VL 53 SU 2 BP S10 EP S10 DI 10.1016/j.freeradbiomed.2012.10.019 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 031RS UT WOS:000310660600017 ER PT J AU Sonnenberg, A Boardman, CR Williams, JE AF Sonnenberg, Amnon Boardman, Charles R. Williams, Jason E. TI Poor preps and piano tuners: Fermi's approach to quantifying the risk for interval colon cancer SO GASTROINTESTINAL ENDOSCOPY LA English DT Letter ID BOWEL PREPARATION; COLONOSCOPY; IMPACT; INADEQUATE; QUALITY C1 [Sonnenberg, Amnon; Boardman, Charles R.] Portland VA Med Ctr, Dept Med, Div Gastroenterol, Portland, OR USA. [Sonnenberg, Amnon; Boardman, Charles R.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Williams, Jason E.] Santa Clara Valley Med Ctr, Dept Med, Div Gastroenterol, San Jose, CA 95128 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, Dept Med, Div Gastroenterol, Portland, OR USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2012 VL 76 IS 5 BP 1083 EP 1084 DI 10.1016/j.gie.2012.07.022 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 036FJ UT WOS:000311011500044 PM 23078944 ER PT J AU Erwin, JA del Rosario, B Payer, B Lee, JT AF Erwin, Jennifer A. del Rosario, Brian Payer, Bernhard Lee, Jeannie T. TI An ex Vivo Model for Imprinting: Mutually Exclusive Binding of Cdx2 and Oct4 as a Switch for Imprinted and Random X-Inactivation SO GENETICS LA English DT Article ID EARLY MOUSE EMBRYOS; CHROMOSOME INACTIVATION; STEM-CELLS; TRANSCRIPTION FACTOR; DOSAGE COMPENSATION; XIST GENE; TSIX; MICE; DIFFERENTIATION; CHOICE AB In the early mammalian embryo, X chromosome inactivation (XCI) achieves dosage parity between males and females for X-linked genes. During mouse development, imprinted paternal XCI is observed first and switches to random XCI in the epiblast but not placental lineages. The mechanism by which this epigenetic switch occurs is currently unknown. Here, we establish an ex vivo model for imprinting and identify a novel trans-acting regulatory factor for imprinted XCI. Using an induced trophoblast stem cell (iTS) model, we show that embryonic stem (ES) cells transdifferentiated into trophoblasts retain partial memory of the XCI imprint. Cdx2, a stem cell factor that determines commitment to the extraembryonic lineage, directly binds Xist and activates expression of Xist RNA in extrembryonic cells. Cdx2 competes with Oct4, a stem cell factor that determines commitment to the embryonic lineage, for overlapping binding sites within Xist. We propose that mutually exclusive binding between Cdx2 and Oct4 in Xist underlies the switch between imprinted and random XCI in the early mouse embryo. C1 [Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu RI Payer, Bernhard/F-7353-2010 OI Payer, Bernhard/0000-0002-4694-2082 FU National Science Foundation; Human Frontiers Science Program Fellowship; National Institutes of Health [GM58839] FX We thank H. Niwa for his generous gift of cdx2-ER plasmid. We also thank the Lee laboratory for general support and many stimulating discussions. This work was funded by a National Science Foundation Fellowship (to J.A.E.), a Human Frontiers Science Program Fellowship (to B. P.), and a National Institutes of Health grant (GM58839) (to J.T.L.). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 52 TC 8 Z9 8 U1 0 U2 5 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2012 VL 192 IS 3 BP 857 EP 868 DI 10.1534/genetics.112.144121 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 033KF UT WOS:000310793900007 PM 22942124 ER PT J AU Jeanne, M Jorgensen, J Labelle-Dumais, C Weng, YC Kauffman, WB de Leau, M Greenberg, SM Rosand, J Favor, J Gould, DB AF Jeanne, Marion Jorgensen, Jeff Labelle-Dumais, Cassandre Weng, Yi-Chinn Kauffman, W. Berkeley de Leau, Michelle Greenberg, Steven M. Rosand, Jonathan Favor, Jack Gould, Douglas B. TI COL4A1 and COL4A2 mutations cause abnormal angiogenesis and genetically modifiable cerebrovascular diseases SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Jeanne, Marion; Jorgensen, Jeff; Labelle-Dumais, Cassandre; Weng, Yi-Chinn; Kauffman, W. Berkeley; de Leau, Michelle; Gould, Douglas B.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp Boston, Boston, MA USA. [Favor, Jack] Helmholtz Zentrum Munchen, Neuherberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1522 EP 1522 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700023 ER PT J AU Newburg, DS Meng, D Nanthakumar, N AF Newburg, David S. Meng, Di Nanthakumar, Nanda TI A novel fucosylated TLR-4 mediates fucose-dependent interkingdom communication between mutualist microbiota and mammalian gut SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Newburg, David S.; Nanthakumar, Nanda] Boston Coll, Chestnut Hill, MA 02167 USA. [Meng, Di] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meng, Di] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1554 EP 1554 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700113 ER PT J AU Khatri, S Maxfield, A Joseph, E Urban, Z AF Khatri, Sandeep Maxfield, Andrew Joseph, Elaine Urban, Zsolt TI Antagonistic regulation of transforming growth factor-beta by fibulin-4a andfibulin-4b is required for cardiovascular and musculoskeletal development in zebrafish SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Glycobiology and American-Society-for-Matrix-Biology CY NOV 11-14, 2012 CL San Diego, CA SP Soc Glycobiol, Amer Soc Matrix Biol C1 [Khatri, Sandeep; Urban, Zsolt] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Maxfield, Andrew] Washington Univ, Sch Med, St Louis, MO USA. [Joseph, Elaine] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2012 VL 22 IS 11 BP 1559 EP 1560 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 027QS UT WOS:000310368700128 ER PT J AU Carter, EA Winter, D Tolman, C Paul, K Hamrahi, V Tompkins, RG Fischman, AJ AF Carter, Edward A. Winter, Daniel Tolman, Crystal Paul, Kasie Hamrahi, Victoria Tompkins, Ronald G. Fischman, Alan J. TI Combination of Radiation and Burn Injury Alters [F-18] 2-Fluoro-2-Deoxy-D-Glucose Uptake in Mice SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID BROWN ADIPOSE-TISSUE; GLUCOSE-UTILIZATION; SUPEROXIDE-DISMUTASE; GAMMA IRRADIATION; THERMAL-INJURY; MORTALITY; MUSCLE; RATS AB Radiation exposure and burn injury have both been shown to alter glucose utilization in vivo. The present study was designed to study the effect of burn injury combined with radiation exposure on glucose metabolism in mice using [F-18] 2-fluoro-2-deoxy-d-glucose ((18)FDG). Groups of male mice weighing approximately 30 g were studied. Group 1 was irradiated with a Cs-137 source (9 Gy). Group 2 received full thickness burn injury on 25% TBSA followed by resuscitation with saline (2 ml, IP). Group 3 received radiation followed 10 minutes later by burn injury. Group 4 were sham-treated controls. After treatment, the mice were fasted for 23 hours and then injected (IV) with 50 mu Ci of (18)FDG. One hour postinjection, the mice were sacrificed, and biodistribution was measured. Positive blood cultures were observed in all groups of animals compared to the shams. Increased mortality was observed after 6 days in the burn plus radiated group as compared to the other groups. Radiation and burn treatments separately or in combination produced major changes in (18)FDG uptake by many tissues. In the heart, brown adipose tissue, and spleen, radiation plus burn produced a much greater increase (P < .0001) in (18)FDG accumulation than either treatment separately. All three treatments produced moderate decreases in (18)FDG accumulation (P < .01) in the brain and gonads. Burn injury, but not irradiation, increased (18)FDG accumulation in skeletal muscle; however, the combination of burn plus radiation decreased (18)FDG accumulation in skeletal muscle. This model may be useful for understanding the effects of burns plus irradiation injury on glucose metabolism and in developing treatments for victims of injuries produced by the combination of burn plus irradiation. (J Burn Care Res 2012;33:723-730) C1 [Carter, Edward A.; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Carter, Edward A.; Paul, Kasie; Hamrahi, Victoria; Fischman, Alan J.] Shriners Hosp Children, Dept Pediat, Boston, MA USA. [Winter, Daniel; Tolman, Crystal; Tompkins, Ronald G.] Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Pediat Gastrointestinal Unit, 114,16th St 114-3503, Charlestown, MA 02129 USA. FU National Institutes of Health [2P50 GM21700-27A]; Shriners Hospital for Children [8470] FX Supported by National Institutes of Health (2P50 GM21700-27A) and Shriners Hospital for Children grant #8470. NR 27 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2012 VL 33 IS 6 BP 723 EP 730 DI 10.1097/BCR.0b013e31825d678f PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 036ML UT WOS:000311030300017 PM 23143615 ER PT J AU Sheridan, RL Neely, AN Castillo, MA Shankowsky, HA Fagan, SP Chung, KK Weber, JM AF Sheridan, Robert L. Neely, Alice N. Castillo, Mayra A. Shankowsky, Heather A. Fagan, Shawn P. Chung, Kevin K. Weber, Joan M. TI A Survey of Invasive Catheter Practices in U.S. Burn Centers SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CRITICALLY-ILL; INFECTIONS AB Burn-specific guidelines for optimal catheter rotation, catheter type, insertion methods, and catheter site care do not exist, and practices vary widely from one burn unit to another. The purpose of this study was to define current practices and identify areas of practice variation for future clinical investigation. An online survey was sent to the directors of 123 U. S. burn centers. The survey consisted of 23 questions related to specific practices in placement and maintenance of central venous catheters (CVCs), arterial catheters, and peripherally inserted central catheters (PICCs). The overall response rate was 36%; response rate from verified centers was 52%. Geographic representation was wide. CVC and arterial catheter replacement varied from every 3 days (24% of sites) to only for overt infection (24% of sites); 23% of sites did not use the femoral position for CVC placement. Nearly 60% of units used some kind of antiseptic catheter. Physicians inserted the majority of catheters, and 22% of sites used nonphysicians for at least some insertions. Ultrasound was routinely used by less than 50% of units. A wide variety of post-insertion dressing protocols were followed. PICCs were used in some critically injured patients in 37% of units; the majority of these users did not rotate PICCs. Thus, it can be surmised that wide practice variation exists among burn centers with regard to insertion and maintenance of invasive catheters. Areas with particular variability that would be appropriate targets of clinical investigation are line rotation protocols, catheter site care protocols, and use of PICCs in acute burns. (J Burn Care Res 2012;33:741-746) C1 [Sheridan, Robert L.; Fagan, Shawn P.; Weber, Joan M.] Shriners Hosp Children, Boston, MA USA. [Neely, Alice N.] Shriners Hosp Children, Cincinnati, OH USA. [Castillo, Mayra A.; Chung, Kevin K.] USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. [Shankowsky, Heather A.] Univ Alberta Hosp, Firefighters Burn Treatment Unit, Edmonton, AB T6G 2B7, Canada. [Sheridan, Robert L.; Fagan, Shawn P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weber, JM (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA USA. NR 12 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2012 VL 33 IS 6 BP 741 EP 746 DI 10.1097/BCR.0b013e318254d4ab PG 6 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 036ML UT WOS:000311030300020 PM 23147213 ER PT J AU Basile, JN Bloch, MJ AF Basile, Jan N. Bloch, Michael J. TI Exposure to Air Pollution Increases the Incidence of Hypertension and Diabetes in Black Women Living in Los Angeles SO JOURNAL OF CLINICAL HYPERTENSION LA English DT Article C1 [Bloch, Michael J.] Univ Nevada, Sch Med, MedSch Associates N, Reno, NV 89557 USA. [Basile, Jan N.] Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Seinsheimer Cardiovasc Hlth Program, Charleston, SC USA. RP Bloch, MJ (reprint author), Univ Nevada, Sch Med, MedSch Associates N, 1500 E 2nd St,Suite 302, Reno, NV 89557 USA. EM mbloch@aol.com NR 1 TC 5 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1524-6175 J9 J CLIN HYPERTENS JI J. Clin. Hypertens. PD NOV PY 2012 VL 14 IS 11 BP 819 EP 820 DI 10.1111/jch.12000 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 031YF UT WOS:000310677900017 PM 23126360 ER PT J AU Lam, HTC O'Toole, TG Arola, PE Kashner, TM Chang, BK AF Lam, Hwai-Tai C. O'Toole, Terry G. Arola, Patricia E. Kashner, T. Michael Chang, Barbara K. TI Factors Associated with the Satisfaction of Millennial Generation Dental Residents SO JOURNAL OF DENTAL EDUCATION LA English DT Article DE dental residents; graduate dental education; Millennial generation; academic environment; academic performance; dental education; productivity; dental assistant; operatory; workload ID LEARNERS PERCEPTIONS SURVEY; EDUCATION AB Data from the 2010 Learners' Perceptions Survey (LPS) administered through the Office of Academic Affiliations, Department of Veterans Affairs (VA) were analyzed to identify factors associated with dental residents' satisfaction with the VA as a clinical training environment. Satisfaction scores were linked to clinic workloads, dental procedure complexity levels, staffing patterns, and facility infrastructure data to explore conditions that may improve residents' satisfaction. Findings supported the construct validity of the LPS survey data and underscored the importance of maintaining optimal ratios of attending dentists, dental assistants, and administrative staff to residents so that each trainee will have opportunities to perform an adequate level of dental workload. As programs strive to improve the quality of graduate dental education, findings from this study are vital for setting curriculum design guidelines and for providing infrastructure support for dental resident education. C1 [Lam, Hwai-Tai C.] US Dept Vet Affairs, Off Policy & Planning, Washington, DC 20006 USA. [Kashner, T. Michael] Loma Linda Univ, Sch Med, Off Acad Affiliat, Loma Linda, CA 92350 USA. [Kashner, T. Michael] Loma Linda Univ, Sch Med, Dept Internal Med, Loma Linda, CA 92350 USA. RP Lam, HTC (reprint author), US Dept Vet Affairs, Off Policy & Planning, Room 540E,1717 H St NE, Washington, DC 20006 USA. EM hwai-tai.lam@va.gov NR 19 TC 4 Z9 4 U1 0 U2 1 PU AMER DENTAL EDUCATION ASSOC PI WASHINGTON PA 1400 K STREET, NW, STE 1100, WASHINGTON, DC 20005 USA SN 0022-0337 J9 J DENT EDUC JI J. Dent. Educ. PD NOV PY 2012 VL 76 IS 11 BP 1416 EP 1426 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 035JF UT WOS:000310941900003 PM 23144476 ER PT J AU Hasegawa, K Obermeyer, Z Milne, LW AF Hasegawa, Kohei Obermeyer, Ziad Milne, Leslie W. TI ECZEMA HERPETICUM SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID DERMATITIS C1 [Hasegawa, Kohei; Obermeyer, Ziad; Milne, Leslie W.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2012 VL 43 IS 5 BP E341 EP E342 DI 10.1016/j.jemermed.2011.05.050 PG 2 WC Emergency Medicine SC Emergency Medicine GA 036NP UT WOS:000311034400021 PM 21852062 ER PT J AU Ring, D AF Ring, David TI Letter Regarding "Adverse Events of Open A1 Pulley Release for Idiopathic Trigger Finger" Reply SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Letter C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2012 VL 37A IS 11 BP 2429 EP 2429 DI 10.1016/j.jhsa.2012.09.003 PG 1 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 035IE UT WOS:000310939200037 ER PT J AU Joseph, RW Eckel-Passow, JE Sharma, R Liu, P Parker, A Jakob, J Buchbinder, E Bassett, RL Davies, MA Hwu, P Atkins, MB Sullivan, RJ AF Joseph, Richard W. Eckel-Passow, Jeanette E. Sharma, Ruchi Liu, Ping Parker, Alexander Jakob, John Buchbinder, Elizabeth Bassett, Roland L. Davies, Michael A. Hwu, Patrick Atkins, Michael B. Sullivan, Ryan J. TI Characterizing the Clinical Benefit of Ipilimumab in Patients Who Progressed on High-dose IL-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE IL-2; ipilimumab; melanoma; immunotherapy ID METASTATIC MELANOMA; INTERLEUKIN-2 THERAPY; SURVIVAL; BRAF AB Ipilimumab improves overall survival (OS) in patients with metastatic melanoma including those previously treated with high-dose interleukin-2 (HD IL-2). The primary objective of this study was to determine if clinical response or progression-free survival (PFS) to HD IL-2 could predict benefit to subsequent ipilimumab. The secondary objective was to further characterize the clinical benefit of ipilimumab in patients who have progressed on HD IL-2. We reviewed the records of all patients with metastatic melanoma who received HD IL-2 at MD Anderson Cancer Center or Beth Israel Deaconess Medical Center from 2003 to 2009 and further identified patients who also received ipilimumab after progressing on HD IL-2. OS to ipilimumab was calculated from the first dose of ipilimumab, determined by Kaplan-Meier analysis, and was compared in patients based on their prior clinical response and PFS to HD IL-2 using the log-rank test. Patients were grouped based on their prior response to HD IL-2 as follows: complete response and partial response, stable disease, and progressive disease. Patients were also grouped and compared by prior PFS to HD IL-2 in > 60 days versus <= 0 days. A total of 208 patients with melanoma were treated with HD IL-2, 130 (63%) received additional systemic therapy after confirmed disease progression, and 48 (23%) received ipilimumab. The clinical benefit of ipilimumab was similar to previously published results (OS, 12.0 mo; PFS, 2.5 mo; response rate, 16.7%). Prior clinical response or PFS to HD IL-2 did not predict benefit to subsequent ipilimumab. Prospective trials of HD IL-2 followed by ipilimumab could potentially identify patients most likely to benefit from a sequential approach of HD IL-2 followed by ipilimumab. C1 [Joseph, Richard W.] Mayo Clin, Div Hematol & Oncol, Jacksonville, FL 32224 USA. [Parker, Alexander] Mayo Clin, Div Epidemiol, Jacksonville, FL 32224 USA. [Eckel-Passow, Jeanette E.; Sharma, Ruchi] Mayo Clin, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA. [Liu, Ping; Jakob, John; Bassett, Roland L.; Davies, Michael A.; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Sullivan, Ryan J.] Massachusetts Gen Hosp, Ctr Canc, Ctr Melanoma, Boston, MA USA. [Atkins, Michael B.] Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. RP Joseph, RW (reprint author), Mayo Clin, Div Hematol & Oncol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM joseph.richard@mayo.edu NR 15 TC 9 Z9 9 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 EI 1537-4513 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 711 EP 715 PG 5 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100007 PM 23090080 ER PT J AU Kurnick, JT Haggerty, TJ Rose, LB Dunn, IS Newton, EE Pandolfi, F AF Kurnick, James T. Haggerty, Timothy J. Rose, Lenora B. Dunn, Ian S. Newton, Estelle E. Pandolfi, Franco TI Combination Therapy With HSP90 Inhibitors and Interferons Synergistically Increases MHC Expression Leading to Enhanced Tumor Cell Recognition; Implications for immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Immune escape; Combination immunotherapy; Tumor associated antigen C1 [Kurnick, James T.; Haggerty, Timothy J.; Rose, Lenora B.; Dunn, Ian S.; Newton, Estelle E.] CytoCure LLC, Beverly, MA USA. [Kurnick, James T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pandolfi, Franco] Catholic Univ Col Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 731 EP 731 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100040 ER PT J AU Gattoni-Celli, S AF Gattoni-Celli, Sebastiano TI Semi-allogeneic Cancer Vaccines SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Cancer vaccine; Active immunotherapy; Combination immunotherapy C1 [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 741 EP 741 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100067 ER PT J AU Duraiswamy, J Freeman, GJ Coukos, G AF Duraiswamy, Jaikumar Freeman, Gordon J. Coukos, George TI Ovarian Tumor-infiltrating T Cells and Myeloid Cells Mediate Immune Suppression Through PD-1/PD-L1 Pathway SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 27th Annual Scientific Meeting of the Society-for-Immunotherapy-of-Cancer (SITC) CY OCT 24-28, 2012 CL North Bethesda, MD SP Soc Immunotherapy Canc (SITC) DE Immunosuppression; Ovarian cancer; PD-1 C1 [Duraiswamy, Jaikumar; Coukos, George] Univ Penn, Ovarian Canc Res Ctr, Philadelphia, PA 19104 USA. [Duraiswamy, Jaikumar; Coukos, George] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2012 VL 35 IS 9 BP 776 EP 776 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 028OF UT WOS:000310431100166 ER PT J AU Saltzman, AJ Paz, YE Rene, AG Green, P Hassanin, A Argenziano, MG Rabbani, L Dangas, G AF Saltzman, Adam J. Paz, Yehuda E. Rene, A. Garvey Green, Philip Hassanin, Ahmed Argenziano, Michael G. Rabbani, Leroy Dangas, George TI Comparison of Surgical Pericardial Drainage With Percutaneous Catheter Drainage for Pericardial Effusion SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE pericardial effusion; pericardiocentesis; pericardiotomy ID CARDIAC-TAMPONADE; SUBXIPHOID PERICARDIOSTOMY; TETRACYCLINE SCLEROSIS; MANAGEMENT; PERICARDIOCENTESIS; DISEASE AB Objective. We sought to investigate the outcomes for different treatments of pericardial effusions. Background. The optimal initial management for symptomatic pericardial effusions remains controversial. Methods. We performed a 3-year retrospective, single-institution study comparing open surgical drainage to percutaneous pericardiocentesis for symptomatic pericardial effusions. Results. Between 2007 and 2009, a total of 193 patients underwent an initial drainage procedure for a pericardial effusion (n = 121 [62.7%] pericardiocentesis; n = 72 [37.3%] open surgical drainage). Compared to those treated with pericardiocentesis, treatment with open surgical drainage was associated with a higher complication rate (4.9% vs 26.4%; P<.0001; odds ratio [OR], 6.9; 95% confidence interval [CI], 2.6-18.2). Treatment with pericardiocentesis was associated with a higher rate of repeat procedures to drain a recurrent effusion compared to open surgical drainage (28.9% vs 2.8%; P<.0001; OR, 14.2; 95% CI, 3.3-61.3). Thirty-day mortality (19.8% surgical group vs 18.1% pericardiocentesis group; P=.8) and long-term survival (P=.4) did not differ between the groups. Conclusion. There is no significant difference in overall mortality between open surgical drainage and percutaneous pericardiocentesis for symptomatic pericardial effusions. There may be more procedural complications following surgical drainage of a pericardial effusion, and a greater need for repeat procedures if the effusion is drained using pericardiocentesis. J INVASIVE CARDIOL 2012;24(11):590-593 C1 [Saltzman, Adam J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Paz, Yehuda E.; Rene, A. Garvey; Green, Philip; Hassanin, Ahmed] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. [Hassanin, Ahmed] Cardiovasc Res Fdn, New York, NY USA. [Argenziano, Michael G.] Columbia Univ, Med Ctr, Dept Surg, New York, NY USA. [Rabbani, Leroy] Columbia Univ, Med Ctr, Div Cardiol, New York, NY USA. [Rabbani, Leroy] Columbia Univ, Med Ctr, Ctr Intervent Vasc Therapy, New York, NY USA. [Dangas, George] Mt Sinai Sch Med, Div Cardiol, New York, NY USA. RP Saltzman, AJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Blake 950, Boston, MA 02114 USA. EM ajsaltzman@partners.org FU NIA NIH HHS [L30 AG040558] NR 19 TC 1 Z9 1 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD NOV PY 2012 VL 24 IS 11 BP 590 EP 593 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 036MJ UT WOS:000311030100014 PM 23117314 ER PT J AU Jelin, AC Kaimal, AJ Kuzniewicz, M Little, SE Cheng, YW Caughey, AB AF Jelin, Angie C. Kaimal, Anjali J. Kuzniewicz, Michael Little, Sarah E. Cheng, Yvonne W. Caughey, Aaron B. TI Preterm preeclampsia: 32 to 37 weeks gestation SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE Neonatal outcomes; preeclampsia; preterm ID RANDOMIZED CONTROLLED-TRIAL; EXPECTANT MANAGEMENT; MILD PREECLAMPSIA; MAGNESIUM-SULFATE; INFANT-MORTALITY; TERM; PREGNANCY; OUTCOMES; BIRTH; WOMEN AB Objective: To evaluate neonatal outcomes in late preterm infants delivered due to preeclampsia. Methods: A retrospective cohort of 3580 infants delivered at 32 0/7 to 36 6/7 weeks gestation was examined. Neonatal outcomes of infants delivered due to preeclampsia were compared with outcomes of infants delivered prematurely due to other etiologies. Multivariate logistic regression was used to analyze the association between preeclampsia and the neonatal outcomes. Results: Infants of women with preeclampsia were more likely to be SGA (26.8% vs. 8.4%). They were also more likely to be admitted to the ICN (54.3% versus 39.0%); however, they were less likely to suffer a neonatal death (2.2% vs. 3.4%). Infants born to women with preeclampsia had similar rates of RDS (19.8% vs. 14.2%). Discussion: Neonatal outcomes in late preterm infants born to preeclamptic mothers are significantly different from outcomes in late preterm neonates delivered due to other indications. C1 [Jelin, Angie C.; Cheng, Yvonne W.] Univ Calif San Francisco, Div Maternal Fetal Med, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Kuzniewicz, Michael] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Little, Sarah E.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. [Caughey, Aaron B.] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR USA. RP Jelin, AC (reprint author), Univ Calif San Francisco, Dept Obstet & Gynecol, 505 Parnassus Ave,Box 0320, San Francisco, CA 94143 USA. EM jelina@peds.ucsf.edu NR 27 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1476-7058 EI 1476-4954 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD NOV PY 2012 VL 25 IS 11 BP 2198 EP 2201 DI 10.3109/14767058.2012.684110 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 036CC UT WOS:000311003000011 PM 22506641 ER PT J AU Murphy, DM Bejar, R Ebert, BL Makrigiorgos, GM AF Murphy, D. M. Bejar, R. Ebert, B. L. Makrigiorgos, G. M. TI COLD-PCR Re-Analysis of Myleodysplastic Syndrome Samples Reveals Previously Undocumented Low-Level Point Mutations in the NRAS Oncogene SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Murphy, D. M.; Bejar, R.; Ebert, B. L.; Makrigiorgos, G. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 654 EP 654 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600087 ER PT J AU Guha, M Makrigiorgos, M AF Guha, M. Makrigiorgos, M. TI Differential Strand Separation at Critical Temperature Reveals Low-Abundance Mutations in Cancer Samples SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Guha, M.; Makrigiorgos, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 699 EP 700 PG 2 WC Pathology SC Pathology GA 025HG UT WOS:000310178600267 ER PT J AU Pecora, ND Bruce, JL Amr, S Mullen, TE Janne, PA Lindeman, NI AF Pecora, N. D. Bruce, J. L. Amr, S. Mullen, T. E. Janne, P. A. Lindeman, N. I. TI A Rapid Assay to Assess EGFR Mutations Leads to Earlier Diagnosis and Treatment of Lung Adenocarcinoma SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Pecora, N. D.; Bruce, J. L.; Lindeman, N. I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amr, S.; Mullen, T. E.] Harvard Univ, Sch Med, Boston, MA USA. [Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 702 EP 702 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600277 ER PT J AU Lin, A Yanagita, M Levinson, S Pache, J Nguyen, Y Chueh, A Lu, B Nguyen, M Maqsodi, B Cayre, YE Miret, JJ Distel, RJ Janne, PA McMaster, G Bers, G Lai, S Nguyen, Q AF Lin, A. Yanagita, M. Levinson, S. Pache, J. Nguyen, Y. Chueh, A. Lu, B. Nguyen, M. Maqsodi, B. Cayre, Y. E. Miret, J. J. Distel, R. J. Jaenne, P. A. McMaster, G. Bers, G. Lai, S. Nguyen, Q. TI Multiplex RNA/miRNA in Situ Detection in Cancer Tumor Cells Captured by an Innovative Circulating Tumor Cell (CTC) Filter- Based Device SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Lin, A.; Levinson, S.; Pache, J.; Nguyen, Y.; Chueh, A.; Lu, B.; Nguyen, M.; Maqsodi, B.; McMaster, G.; Bers, G.; Lai, S.; Nguyen, Q.] Affymetrix Inc, Santa Clara, CA USA. [Yanagita, M.; Jaenne, P. A.] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Cayre, Y. E.] ScreenCell, Paris, Lie De, France. [Distel, R. J.] Dana Farber Canc Inst, Ctr Clin &Translat Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 725 EP 726 PG 2 WC Pathology SC Pathology GA 025HG UT WOS:000310178600369 ER PT J AU Castellanos-Rizaldos, E Liu, P Milbury, CA Guha, M Brisci, A Cremonesi, L Ferrari, M Mamon, H Makrigiorgos, GM AF Castellanos-Rizaldos, E. Liu, P. Milbury, C. A. Guha, M. Brisci, A. Cremonesi, L. Ferrari, M. Mamon, H. Makrigiorgos, G. M. TI Temperature-Tolerant Cold-PCR, a Temperature Flexible Approach that Yields Reproducible Mutation Enrichment SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Castellanos-Rizaldos, E.; Liu, P.; Milbury, C. A.; Guha, M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Brisci, A.; Cremonesi, L.; Ferrari, M.] Ist Sci San Raffaele, I-20132 Milan, Italy. [Mamon, H.; Makrigiorgos, G. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ferrari, Maurizio/D-9107-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 728 EP 728 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600379 ER PT J AU Spencer, D Vallania, F Sehn, JK Mitra, RD Duncavage, EJ AF Spencer, D. Vallania, F. Sehn, J. K. Mitra, R. D. Duncavage, E. J. TI Sensitivity and Limit of Detection of Next-Generation Sequencing for Detecting Somatic Mutations in Heterogeneous Samples SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Spencer, D.; Vallania, F.; Mitra, R. D.; Duncavage, E. J.] Washington Univ, St Louis, MO USA. [Sehn, J. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 732 EP 732 PG 1 WC Pathology SC Pathology GA 025HG UT WOS:000310178600393 ER PT J AU Sehn, J Spencer, D Mitre, R Duncavage, E AF Sehn, J. Spencer, D. Mitre, R. Duncavage, E. TI A Comparison of Indel Detection Software Tools in Targeted Clinical Next Generation Sequencing Data SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY OCT 25-27, 2012 CL Long Beach, CA SP Assoc Mol Pathol C1 [Sehn, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spencer, D.; Mitre, R.; Duncavage, E.] Washington Univ, Sch Med, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2012 VL 14 IS 6 BP 734 EP 735 PG 2 WC Pathology SC Pathology GA 025HG UT WOS:000310178600403 ER PT J AU Korkmaz, OT Tuncel, N Tekin, N Sener, E Akyuz, F Inal, M AF Korkmaz, Orhan Tansel Tuncel, Nese Tekin, Neslihan Sener, Erol Akyuz, Fahrettin Inal, Mine TI Antioxidant and anti-apoptotic activity of Vasoactive Intestinal Peptide (VIP) against 6-hydroxy dopamine toxicity in the rat corpus striatum SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) DE Vasoactive intestinal peptide; Parkinson's Disease; DNA fragmentation; oxidative damage; 6-OHDA; nitric oxide C1 [Korkmaz, Orhan Tansel] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Korkmaz, Orhan Tansel] VA Boston Healthcare Syst, Res GRECC, Boston, MA USA. [Korkmaz, Orhan Tansel; Tuncel, Nese; Tekin, Neslihan] Eskisehir Osmangazi Univ, Fac Med, Dept Physiol, TR-26480 Eskisehir, Turkey. [Akyuz, Fahrettin; Inal, Mine] Eskisehir Osmangazi Univ, Fac Med, Dept Biochem, TR-26480 Eskisehir, Turkey. [Sener, Erol] Anadolu Univ, Fac Pharm, Dept Analyt Chem, TR-26470 Eskisehir, Turkey. NR 0 TC 0 Z9 0 U1 1 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S200 EP S200 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600456 ER PT J AU Vu, J Mulugeta, M Larauche, M Waschek, JA Tache, Y Pisegna, J Germano, PM AF Vu, John Mulugeta, Million Larauche, Muriel Waschek, James A. Tache, Yvette Pisegna, JosephR. Germano, Patrizia M. TI VIP deficiency has a protective effect against Dextran Sulfate Sodium (DSS) induced colitis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Vu, John; Mulugeta, Million; Larauche, Muriel; Tache, Yvette; Pisegna, JosephR.; Germano, Patrizia M.] Univ Calif Los Angeles, Div Gastroenterol & Hepatol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Waschek, James A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S200 EP S201 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600457 ER PT J AU Vu, J Mulugeta, M Larauche, M Waschek, JA Tache, Y Pisegna, JR Germano, PM AF Vu, John Mulugeta, Million Larauche, Muriel Waschek, James A. Tache, Yvette Pisegna, Joseph R. Germano, Patrizia M. TI VIP deficiency has a protective effect against Dextran Sulfate Sodium (DSS) induced colitis SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Meeting Abstract CT Summer Neuropeptide Conference / Meeting of the European-Neuropeptide-Club (ENC) CY MAY 22-25, 2011 CL Boston, MA SP European Neuropeptide Club (ENC) C1 [Vu, John; Mulugeta, Million; Larauche, Muriel; Tache, Yvette; Pisegna, Joseph R.; Germano, Patrizia M.] Univ Calif Los Angeles, Div Gastroenterol & Hepatol, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Waschek, James A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD NOV PY 2012 VL 48 SU 1 BP S193 EP S193 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 030BC UT WOS:000310541600442 ER PT J AU Day, ML Koka, K Delgutte, B AF Day, Mitchell L. Koka, Kanthaiah Delgutte, Bertrand TI Neural encoding of sound source location in the presence of a concurrent, spatially separated source SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE azimuth; interaural time difference; interaural level difference; inferior colliculus; rabbit ID INTERAURAL TIME DIFFERENCES; AUDITORY CORTICAL-NEURONS; LATERAL SUPERIOR OLIVE; INFERIOR COLLICULUS; RECEPTIVE-FIELDS; DIRECTIONAL SENSITIVITY; RESPONSE PROPERTIES; LOCALIZATION CUES; NOISE; RABBIT AB Day ML, Koka K, Delgutte B. Neural encoding of sound source location in the presence of a concurrent, spatially separated source. J Neurophysiol 108: 2612-2628, 2012. First published August 22, 2012; doi:10.1152/jn.00303.2012.-In the presence of multiple, spatially separated sound sources, the binaural cues used for sound localization in the horizontal plane become distorted from the cues from each sound in isolation, yet localization in everyday multisource acoustic environments remains robust. We examined changes in the azimuth tuning functions of inferior colliculus (IC) neurons in un-anesthetized rabbits to a target broadband noise when a concurrent broadband noise interferer was presented at different locations in virtual acoustic space. The presence of an interferer generally degraded sensitivity to target azimuth and distorted the shape of the tuning function, yet most neurons remained significantly sensitive to target azimuth and maintained tuning function shapes somewhat similar to those for the target alone. Using binaural cue manipulations in virtual acoustic space, we found that single-source tuning functions of neurons with high best frequencies (BFs) were primarily determined by interaural level differences (ILDs) or monaural level, with a small influence of interaural time differences (ITDs) in some neurons. However, with a centrally located interferer, the tuning functions of most high-BF neurons were strongly influenced by ITDs as well as ILDs. Model-based analysis showed that the shapes of these tuning functions were in part produced by decorrelation of the left and right cochlea-induced envelopes that occurs with source separation. The strong influence of ITD on the tuning functions of high-BF neurons poses a challenge to the "duplex theory" of sound localization and suggests that ITD may be important for localizing high-frequency sounds in multisource environments. C1 [Day, Mitchell L.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. [Day, Mitchell L.; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Koka, Kanthaiah] Univ Colorado, Sch Med, Dept Physiol & Biophys, Denver, CO USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Day, ML (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA. EM day@meei.harvard.edu OI Day, Mitchell/0000-0002-2754-234X; , /0000-0003-1349-9608 FU National Institute on Deafness and Other Communication Disorders [R01 DC002258, P30 DC005209, R01 DC011555] FX This work was supported by National Institute on Deafness and Other Communication Disorders Grants R01 DC002258 and P30 DC005209 (B. Delgutte) and R01 DC011555 (D. J. Tollin). NR 49 TC 11 Z9 12 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2012 VL 108 IS 9 BP 2612 EP 2628 DI 10.1152/jn.00303.2012 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 032GM UT WOS:000310702200025 PM 22914651 ER PT J AU Elder, GA Dorr, NP De Gasperi, R Sosa, MAG Shaughness, MC Maudlin-Jeronimo, E Hall, AA McCarron, RM Ahlers, ST AF Elder, Gregory A. Dorr, Nathan P. De Gasperi, Rita Sosa, Miguel A. Gama Shaughness, Michael C. Maudlin-Jeronimo, Eric Hall, Aaron A. McCarron, Richard M. Ahlers, Stephen T. TI Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE blast; PTSD; rat; stathmin 1; TBI ID STARTLE RESPONSE; INTRACRANIAL-PRESSURE; BEHAVIORAL CRITERIA; VIETNAM VETERANS; SERUM BIOMARKER; WAR VETERANS; MOUSE MODEL; MICE; OVERPRESSURE; PATHOLOGY AB Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety of PTSD-related behavioral traits that were present many months after the blast exposure, including increased anxiety, enhanced contextual fear conditioning, and an altered response in a predator scent assay. We also found elevation in the amygdala of the protein stathmin 1, which is known to influence the generation of fear responses. Because the blast overpressure injuries occurred while animals were under general anesthesia, our results suggest that a blast-related mTBI exposure can, in the absence of any psychological stressor, induce PTSD-related traits that are chronic and persistent. These studies have implications for understanding the relationship of PTSD to mTBI in the population of veterans returning from the wars in Iraq and Afghanistan. C1 [Elder, Gregory A.] James J Peters Dept Vet Affairs Med Ctr, Neurol Serv, Bronx, NY USA. [De Gasperi, Rita; Sosa, Miguel A. Gama] James J Peters Dept Vet Affairs Med Ctr, Res & Dev Serv, Bronx, NY USA. [Elder, Gregory A.; Dorr, Nathan P.; De Gasperi, Rita; Sosa, Miguel A. Gama] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Elder, Gregory A.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A.; McCarron, Richard M.; Ahlers, Stephen T.] USN, Dept Neurotrauma, Operat & Undersea Med Directorate, Med Res Ctr, Silver Spring, MD USA. [Elder, Gregory A.; De Gasperi, Rita; Sosa, Miguel A. Gama] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA. RP Elder, GA (reprint author), James J Peters VA Med Ctr, Neurol Serv 3E16, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM gregory.elder@va.gov FU Department of Veterans Affairs [1I01RX000179-01] FX This work was supported by grant 1I01RX000179-01 from the Department of Veterans Affairs. NR 54 TC 54 Z9 54 U1 2 U2 24 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV PY 2012 VL 29 IS 16 BP 2564 EP 2575 DI 10.1089/neu.2012.2510 PG 12 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 035CS UT WOS:000310920900005 PM 22780833 ER PT J AU Guthrie, D Peacock, ZS Sadow, P Dodson, TB August, M AF Guthrie, David Peacock, Zachary S. Sadow, Peter Dodson, Thomas B. August, Meredith TI Preoperative Incisional and Intraoperative Frozen Section Biopsy Techniques Have Comparable Accuracy in the Diagnosis of Benign Intraosseous Jaw Pathology SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ODONTOGENIC KERATOCYSTS; ENUCLEATION AB Purpose: To compare the accuracy of intraoperative frozen section (FS) and preoperative incisional biopsy (IB) techniques to diagnose benign intraosseous jaw lesions. Materials and Methods: This is a retrospective cohort study composed of subjects with benign intraosseous jaw lesions. The predictor variable was the technique for establishing a preliminary diagnosis of the lesion, preoperative IB or intraoperative FS. The outcome variable was the accuracy of the biopsy technique when compared with the final histologic diagnosis and was classified as concordant or discordant. The comparative diagnostic accuracy of the techniques was assessed with the chi(2) test. Results: A total of 71 subjects met inclusion criteria. The mean age was 39 years (range, 5 to 85 years), and 58% (41) were male patients. Of the subjects, 20 (28%) underwent IB. In 14 (70%) of these, the results of biopsy agreed with the final diagnosis. 51 (72%) underwent intraoperative FS and in 31 (62%) of these, the results of biopsy agreed with the final diagnosis. The difference in diagnostic accuracy between IB (70%) and FS (61%) was statistically insignificant (P = .48). Sources of biopsy error included sampling error (46%), insufficient epithelial tissue (15%), inflammation (15%), pathologist's experience (8%), and artifact (4%). Conclusions: Preoperative IB and intraoperative FS provide comparable accuracy of diagnosis in patients with benign intraosseous jaw pathology. Sampling error was the most common reason for discordant results. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:2566-2572, 2012 C1 [Guthrie, David; Peacock, Zachary S.; August, Meredith] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Guthrie, David; Peacock, Zachary S.; Dodson, Thomas B.; August, Meredith] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Sadow, Peter] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Sadow, Peter] Harvard Univ, Sch Med, Boston, MA USA. RP Guthrie, D (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. EM guthrie.10@gmail.com NR 15 TC 6 Z9 7 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2012 VL 70 IS 11 BP 2566 EP 2572 DI 10.1016/j.joms.2011.11.023 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 033HD UT WOS:000310784000027 PM 22285333 ER PT J AU Peacock, ZS Resnick, CM Susarla, SM Faquin, WC Rosenberg, AE Nielsen, GP Schwab, JH Hornicek, F Ebb, DH Dodson, TB Kaban, LB AF Peacock, Zachary S. Resnick, Cory M. Susarla, Srinivas M. Faquin, William C. Rosenberg, Andrew E. Nielsen, Gunnlaugur P. Schwab, Joseph H. Hornicek, Francis Ebb, David H. Dodson, Thomas B. Kaban, Leonard B. TI Do Histologic Criteria Predict Biologic Behavior of Giant Cell Lesions? SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID REPARATIVE GRANULOMA; TUMOR; JAWS; BONE; METASTASES AB Purpose: To determine whether the clinical behavior of giant cell lesions (GCLs) or their anatomic location can be differentiated by histologic criteria alone. Materials and Methods: We performed a retrospective study of patients with GCLs treated at Massachusetts General Hospital between 1993 and 2008. Predictor variables were histologic parameters: number of giant cells (GCs) per high-power field, number of nuclei per GC, GC size, stromal cellularity, stromal type, presence of hemorrhage and reactive osteoid, and blinded pathologists' prediction of location and behavior. Outcome variables were clinical behavior (aggressive or nonaggressive) and GCL location, that is, maxillofacial (MF) or axial/appendicular (AA). Descriptive and bivariate statistics were computed with statistical significance set at P <= .05. Results: The sample included 88 subjects: 41 MF GCLs (35 aggressive) and 47 AA GCLs (28 aggressive). Aggressive AA lesions had more GCs per high-power field, larger mean GC size, and increased stromal cellularity, and they more frequently had a mononuclear stroma when compared with aggressive MF lesions (P < .05). There were no significant histologic differences between aggressive and nonaggressive MF lesions or between nonaggressive MF and nonaggressive AA lesions. Aggressive AA lesions had more nuclei/GC than nonaggressive AA lesions (P = .03). Using histologic criteria only, blinded pathologists predicted clinical behavior in only 45% of cases (kappa = 0.19, P = .09). They predicted a lesion's location in 82% of cases with fair agreement (kappa = 0.44, P < .01). Conclusions: Results of this study indicate that histologic differences between aggressive and nonaggressive GCLs are insufficient for pathologists to differentiate them consistently regardless of location. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:2573-2580, 2012 C1 [Peacock, Zachary S.; Dodson, Thomas B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, Boston, MA 02114 USA. [Hornicek, Francis] Harvard Univ, Sch Med, Dept Orthoped Surg, Orthoped Oncol Serv,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Faquin, William C.; Rosenberg, Andrew E.; Nielsen, Gunnlaugur P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ebb, David H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Ctr Appl Clin Invest, WRN 1201, Boston, MA 02114 USA. EM zpeacock@partners.org OI Susarla, Srinivas/0000-0003-0155-8260; Resnick, Cory/0000-0002-6391-9618 FU General Hospital Department of Oral and Maxillofacial Surgery's Center for Applied Clinical Investigation and Education and Research Fund; Department of Orthopedic Surgery; Massachusetts General Physicians Organization FX Supported by Massachusetts General Hospital Department of Oral and Maxillofacial Surgery's Center for Applied Clinical Investigation and Education and Research Fund, Department of Orthopedic Surgery, and Massachusetts General Physicians Organization. NR 28 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2012 VL 70 IS 11 BP 2573 EP 2580 DI 10.1016/j.joms.2011.12.005 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 033HD UT WOS:000310784000028 PM 22365980 ER PT J AU Papadaki, ME Kaban, LB Troulis, MJ AF Papadaki, Maria E. Kaban, Leonard B. Troulis, Maria J. TI Minipig Model of Maxillary Distraction Osteogenesis: Immunohistochemical and Histomorphometric Analysis of the Sequence of Osteogenesis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SUTURAL EXPANSION OSTEOGENESIS; MANDIBULAR DISTRACTION; BONE-FORMATION; MIDFACE ADVANCEMENT; GRADUAL DISTRACTION; CLEFT-PALATE; FOLLOW-UP; DEVICE; TRANSPORT; DOGS AB Purpose: To document the sequence of bone formation in a minipig model of Le Fort I distraction osteogenesis (DO) using immunohistochemistry and histomorphometry. Materials and Methods: Female Yucatan minipigs (N = 9) in the mixed-dentition stage underwent bilateral maxillary DO. The distraction protocol was 0 days of latency, with a distraction rate of 1 mm/d for 12 days and 24 days of fixation. Specimens were harvested and divided between the central incisors (18 hemi-maxillae) at the end of DO (n = 6), at mid-fixation (n = 6), and at the end of fixation (n = 6). Sections, including the advancement zone, were stained with hematoxylin-eosin, collagen II, CD34, proliferating cell nuclear antigen, and tartrate-resistant acid phosphatase. Light and fluorescence microscope images (original magnification x200) were obtained, and percentage of surface area (PSA) of the advancement zone occupied by fibrous tissue, vessels, proliferating cells, osteoid, and bone was determined. An intact maxilla served as the control. Results: At the end of DO, in the advancement zone, the PSA (mean values) of proliferating cells was 33.16%; fibrous tissue, 52%; vessels, 4.35%; and new bone, 5.45%. At the end of fixation, the PSA of proliferating cells decreased to 10.53%, fibrous tissue to 2.3%, and vessels to 1.5% whereas the PSA of new bone increased to 44.9%. Conclusions: The results of this study indicate that the progression of osteogenesis in the maxillary DO wound begins with intense cellular proliferation and vascular fibrous tissue formation and progresses to mature, cancellous bone by the end of fixation. The PSA occupied by mature bone is significantly less than in the control maxilla at the end of fixation. This is consistent with the sequence in the mandibular DO wound. This is a US government work. There are no restrictions on its use. Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 70:2629-2640, 2012 C1 [Papadaki, Maria E.; Kaban, Leonard B.; Troulis, Maria J.] Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Papadaki, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. EM mpapadaki@partners.org FU AO Foundation [03-K69]; Hanson Foundation (Boston, MA); AO/Synthes/MGH Fellowship in Pediatric Oral and Maxillofacial Surgery FX Funded by the AO Foundation (grant 03-K69), the Hanson Foundation (Boston, MA), and the AO/Synthes/MGH Fellowship in Pediatric Oral and Maxillofacial Surgery. NR 42 TC 1 Z9 1 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2012 VL 70 IS 11 BP 2629 EP 2640 DI 10.1016/j.joms.2012.01.030 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 033HD UT WOS:000310784000038 PM 22516839 ER PT J AU Winter, HS Mossialos, E Naci, H Chandra, A Salojee, H Yamashiro, Y Bhutta, ZA Uauy, R Corvalan, C AF Winter, Harland S. Mossialos, Elias Naci, Huseyin Chandra, Amitabh Salojee, Haroon Yamashiro, Yuichiro Bhutta, Zulfiqar A. Uauy, Ricardo Corvalan, Camila TI The Economics of Health Care Delivery SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID UPDATED SYSTEMATIC ANALYSIS; DEVELOPING-COUNTRIES; CHILD UNDERNUTRITION; BIRTH-WEIGHT; EARLY-LIFE; MORTALITY; CONSEQUENCES; GROWTH; COHORT; INTERVENTIONS C1 [Winter, Harland S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhutta, Zulfiqar A.] Aga Khan Univ, Karachi, Pakistan. [Chandra, Amitabh] Harvard Univ, Harvard Kennedy Sch Govt, Cambridge, MA 02138 USA. [Yamashiro, Yuichiro] Juntendo Univ, Grad Sch Med, Probiot Res Lab, Tokyo, Japan. [Salojee, Haroon] Univ Witwatersrand, Div Community Paediat, Johannesburg, South Africa. [Mossialos, Elias; Naci, Huseyin] Univ London London Sch Econ & Polit Sci, London WC2A 2AE, England. [Uauy, Ricardo] Pontificia Univ Catolica Chile, Sch Med, Div Pediat, Santiago, Chile. [Corvalan, Camila] Univ Chile, INTA, Santiago, Chile. RP Winter, HS (reprint author), Massachusetts Gen Hosp, 175 Cambridge St,CRPZ 5-560, Boston, MA 02114 USA. EM HWINTER@partners.org NR 54 TC 0 Z9 0 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2012 VL 55 IS 5 BP 482 EP 488 DI 10.1097/MPG.0b013e318272af3b PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 030LH UT WOS:000310571700008 PM 22995868 ER PT J AU Kelley-Quon, LI Jen, HC Ziring, DA Gupta, N Kirschner, BS Ferry, GD Cohen, SA Winter, HS Heyman, MB Gold, BD Shew, SB AF Kelley-Quon, Lorraine I. Jen, Howard C. Ziring, David A. Gupta, Neera Kirschner, Barbara S. Ferry, George D. Cohen, Stanley A. Winter, Harland S. Heyman, Melvin B. Gold, Benjamin D. Shew, Stephen B. TI Predictors of Proctocolectomy in Children With Ulcerative Colitis SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE colectomy; proctocolectomy; ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; POUCH-ANAL ANASTOMOSIS; NATURAL-HISTORY; ACTIVITY INDEX; SURGERY; COHORT; ONSET; RISK; IBD; THERAPY AB Objectives: Few clinical predictors are associated with definitive proctocolectomy in children with ulcerative colitis (UC). The purpose of the present study was to identify clinical predictors associated with surgery in children with UC using a disease-specific database. Methods: Children diagnosed with UC at age <18 years were identified using the Pediatric Inflammatory Bowel Disease Consortium (PediIBDC) database. Demographic and clinical variables from January 1999 to November 2003 were extracted alongside incidence and surgical staging. Results: Review of the PediIBDC database identified 406 children with UC. Approximately half were girls (51%) with an average age at diagnosis of 10.6 +/- 4.4 years in both boys and girls. Average follow-up was 6.8 (+/- 4.0) years. Of the 57 (14%) who underwent surgery, median time to surgery was 3.8 (interquartile range 4.9) years after initial diagnosis. Children presenting with weight loss (hazard ratio [HR] 2.55, 99% confidence interval [CI] 1.21-5.35) or serum albumin <3.5 g/dL (HR 6.05, 99% CI 2.15-17.04) at time of diagnosis and children with a first-degree relative with UC (HR 1.81, 99% CI 1.25-2.61) required earlier surgical intervention. Furthermore, children treated with cyclosporine (HR 6.11, 99% CI 3.90-9.57) or tacrolimus (HR 3.66, 99% CI 1.60-8.39) also required earlier surgical management. Other symptoms, laboratory tests, and medical therapies were not predictive for need of surgery. Conclusion: Children with UC presenting with hypoalbuminemia, weight loss, a family history of UC, and those treated with calcineurin inhibitors frequently require restorative proctocolectomy for definitive treatment. Early identification and recognition of these factors should be used to shape treatment goals and initiate multidisciplinary care at the time of diagnosis. C1 [Kelley-Quon, Lorraine I.; Jen, Howard C.; Ziring, David A.; Shew, Stephen B.] Univ Calif San Francisco, Mattel Childrens Hosp, San Francisco, CA 94143 USA. [Gupta, Neera; Heyman, Melvin B.] Univ Calif San Francisco, UCSF Benioff Childrens Hosp, San Francisco, CA 94143 USA. [Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. [Ferry, George D.] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. [Cohen, Stanley A.] Childrens Healthcare Atlanta, Childrens Ctr Digest Healthcare, Atlanta, GA USA. [Winter, Harland S.] MassGen Hosp Children, Boston, MA USA. [Gold, Benjamin D.] Emory Univ, Sch Med, Atlanta, GA USA. RP Shew, SB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Mattel Childrens Hosp, Div Pediat Surg, 10833 Le Conte Ave,CHS Bldg,MC 957098, Los Angeles, CA 90095 USA. EM sshew@mednet.ucla.edu FU NIH [DK060617, DK077734, HD052885]; Abbott; Janssen Biotech; Given Imaging; Janssen; UCB; Astra Zeneca; UCB Pharma; Nutricia; Prometheus Labs; Takeda Pharmaceuticals North America; Pediatric Inflammatory Bowel Disease Foundation FX L.K.Q. is a 2010-2012 Robert Wood Johnson Foundation Community Health Leader. M. H. is supported in part by NIH grant DK060617. N.G. is supported in part by NIH grant DK077734. B. K. is supported in part by grants from Abbott and Janssen Biotech. S. C. is supported in part by grants from Given Imaging, Janssen, Abbott, UCB, and Astra Zeneca. H. W. is supported in part by grants from Janssen, UCB Pharma, Nutricia, and Prometheus Labs. B. G. is supported in part by grants from Takeda Pharmaceuticals North America. S. S. is supported in part by NIH grant HD052885. The other authors report no conflicts of interest.; The authors thank the Pediatric Inflammatory Bowel Disease Foundation for sponsoring the Consortium and this work. NR 22 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2012 VL 55 IS 5 BP 534 EP 540 DI 10.1097/MPG.0b013e3182619d26 PG 7 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 030LH UT WOS:000310571700017 PM 22684351 ER PT J AU Guarino, A Winter, H Sandhu, B Quak, SH Lanata, C AF Guarino, Alfredo Winter, Harland Sandhu, Bhupinder Quak, Seng Hock Lanata, Claudio TI Acute Gastroenteritis Disease: Report of the FISPGHAN Working Group SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID ROTAVIRUS VACCINATION; MORTALITY; DIARRHEA; CHILDREN C1 [Guarino, Alfredo] Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy. [Winter, Harland] MassGen Hosp Children, Boston, MA USA. [Sandhu, Bhupinder] Bristol Royal Hosp Children, Dept Paediat Gastroenterol, Bristol, Avon, England. [Quak, Seng Hock] Natl Univ Singapore Hosp, Dept Pediat, Singapore, Singapore. [Lanata, Claudio] Inst Invest Nutr, Lima, Peru. RP Guarino, A (reprint author), Univ Naples Federico II, Dept Pediat, I-80131 Naples, Italy. EM alfguari@unina.it NR 16 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2012 VL 55 IS 5 BP 621 EP 626 DI 10.1097/MPG.0b013e318272b5e2 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 030LH UT WOS:000310571700034 PM 22983379 ER PT J AU Nansel, TR Haynie, DL Lipsky, LM Laffel, LMB Mehta, SN AF Nansel, Tonja R. Haynie, Denise L. Lipsky, Leah M. Laffel, Lori M. B. Mehta, Sanjeev N. TI Multiple Indicators of Poor Diet Quality in Children and Adolescents with Type 1 Diabetes Are Associated with Higher Body Mass Index Percentile but not Glycemic Control SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Diabetes mellitus, type 1; Diet; Disease management; Body weight ID NUTRIENT-RICH FOODS; BLOOD-GLUCOSE CONTROL; WEIGHT-GAIN; COMPLICATIONS TRIAL; INSULIN THERAPY; RISK-FACTORS; US CHILDREN; YOUTH; PREVALENCE; NUTRITION AB Background Diet is a cornerstone of type 1 diabetes treatment, and poor diet quality may affect glycemic control and other health outcomes. Yet diet quality in children and adolescents with type 1 diabetes remains understudied. Objective To evaluate multiple indicators of diet quality in children and adolescents with type I diabetes and their associations with hemoglobin A1c and body mass index percentile. Design In this cross-sectional study, participants completed 3-day diet records, and data were abstracted from participants' medical records. Diet quality indicators included servings of fruit, vegetables, and whole grains; Healthy Eating Index-2005 (HEI-2005) score; Nutrient Rich Foods 9.3 score (NRF 9.3); and glycemic index. Participants/setting Children and adolescents with type >= 1 diabetes year, aged 8 to 18 years, were recruited at routine clinic visits. Of 291 families enrolled, 252 provided diet data. Statistical analyses Associations of diet quality indicators to HbA1c and body mass index percentile were examined using analysis of covariance and multiple linear regression. Results Participants demonstrated low adherence to dietary guidelines; mean HEI-2005 score was 53.4 +/- 11.0 (range=26.7 to 81.2). Intake of fruit, vegetables, and whole grains was less than half the recommended amount. Almost half of the participants' daily energy intake was derived from refined-grain products, desserts, chips, and sweetened beverages. Higher fruit (P=0.04) and whole-grain (P=0.03) intake were associated with lower HbA1c in unadjusted, but not adjusted analyses; vegetable intake, HEI-2005 score, NRF 9.3 score, and glycemic index were not associated with HbA1c. Higher fruit (P=0.01) and whole-grain (P=0.04) intake and NRF 9.3 score (P=0.02), but not other diet quality indicators, were associated with lower body mass index percentile in adjusted analyses. Conclusions Data demonstrate poor diet quality in youth with type 1 diabetes and provide support for the importance of diet quality for weight management. Future research on determinants of dietary intake and methods to promote improved diet quality would be useful to inform clinical care. J Acad Nutr Diet. 2012;112:1728-1735. C1 [Nansel, Tonja R.; Haynie, Denise L.; Lipsky, Leah M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Laffel, Lori M. B.] Harvard Univ, Sch Med, Pediat Adolescent & Young Adult Sect, Boston, MA USA. [Laffel, Lori M. B.; Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, 6100 Execut Blvd,Room 7B13R,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract no. HHSN267200703434C). NR 54 TC 19 Z9 21 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2012 VL 112 IS 11 BP 1728 EP 1735 DI 10.1016/j.jand.2012.08.029 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033RT UT WOS:000310819200005 PM 23102173 ER PT J AU Tse, J Nansel, TR Haynie, DL Mehta, SN Laffel, LMB AF Tse, Julia Nansel, Tonja R. Haynie, Denise L. Mehta, Sanjeev N. Laffel, Lori M. B. TI Disordered Eating Behaviors Are Associated with Poorer Diet Quality in Adolescents with Type 1 Diabetes SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS LA English DT Article DE Type 1 diabetes; Disordered eating; Dietary quality; Diabetes management; Diabetes Eating Problem Survey ID COMPLICATIONS TRIAL; BODY-WEIGHT; OVERWEIGHT; CHILDREN; MELLITUS; BARRIERS; FEMALES; OBESITY; ADULTS; GIRLS AB Disordered eating behaviors may pose a risk for poor long-term health outcomes in patients with type 1 diabetes. This cross-sectional study examined associations of disordered eating behaviors with diet quality, diet-related attitudes, and diabetes management in adolescents with type 1 diabetes (N=151, 48% female). Participants, recruited July 2008 through February 2009, completed 3-day diet records and survey measures, including the Diabetes Eating Problem Survey (DEPS) and measures of eating-related attitudes. Biomedical data were obtained from medical records. Participants scoring more than 1 standard deviation above the mean DEPS were classified as at risk for disordered eating. The Healthy Eating Index-2005 was calculated to assess diet quality. Analysis of covariance was used to test for differences between risk groups in diet quality, eating attitudes, and diabetes management controlling forage, sex, and body mass index (BMI) percentile. Youth at risk for disordered eating were more likely to be overweight/obese than those at low risk (59.1% vs 31.8%, P=0.01). The at-risk group had poorer diet quality (P=0.003) as well as higher intake of total fat (P=0.01) and saturated fat (P=0.007) compared with the low-risk group. The at-risk group reported lower self-efficacy (P=0.005), greater barriers (P<0.001), and more negative outcome expectations (P<0.001) for healthful eating, as well as worse dietary satisfaction (P=0.004). The at-risk group had lower diabetes adherence (P<0.01), less-frequent blood glucose monitoring (P<0.002), and higher hemoglobin A1c (P<0.001). The constellation of excess weight, poorer dietary intake, and poorer diabetes management associated with youth at risk for disordered eating suggests potential risk of future poor health outcomes. Attention should be given to healthful weight management, especially among overweight youth with type 1 diabetes. J Acad Nutr Diet 2012;112:1810-1814. C1 [Tse, Julia; Nansel, Tonja R.; Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Mehta, Sanjeev N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02115 USA. [Laffel, Lori M. B.] Harvard Univ, Sch Med, Adolescent & Young Adult Sect, Boston, MA 02115 USA. RP Nansel, TR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bldg 6100,Room 7805,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract number HHSN267200703434C. NR 28 TC 11 Z9 11 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-2672 J9 J ACAD NUTR DIET JI J. Acad. Nutr. Diet. PD NOV PY 2012 VL 112 IS 11 BP 1810 EP 1814 DI 10.1016/j.jand.2012.06.359 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 033RT UT WOS:000310819200014 PM 23102180 ER PT J AU Gray, E AF Gray, Emily TI Coming of Age on Zoloft: How Antidepressants Cheered Us Up, Let Us Down, and Changed Who We Are SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Gray, Emily] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gray, E (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ekgray@partners.org NR 1 TC 0 Z9 0 U1 1 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD NOV PY 2012 VL 51 IS 11 BP 1222 EP 1223 DI 10.1016/j.jaac.2012.09.007 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 035IF UT WOS:000310939300017 ER PT J AU Jalili, A Wagner, C Pashenkov, M Pathria, G Mertz, KD Widlund, HR Lupien, M Brunet, JP Golub, TR Stingl, G Fisher, DE Ramaswamy, S Wagner, SN AF Jalili, Ahmad Wagner, Christine Pashenkov, Mikhail Pathria, Gaurav Mertz, Kirsten D. Widlund, Hans R. Lupien, Mathieu Brunet, Jean-Philippe Golub, Todd R. Stingl, Georg Fisher, David E. Ramaswamy, Sridhar Wagner, Stephan N. TI Dual Suppression of the Cyclin-Dependent Kinase Inhibitors CDKN2C and CDKN1A in Human Melanoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DOWN-REGULATION; RESISTANCE; BRAF; P16(INK4A); ACTIVATION; EXPRESSION; P21(CIP1); MUTATION; GROWTH; MICE AB Resistance to BRAF(V600E) inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. To identify downstream effectors of MAPK signaling that could be used as potential additional therapeutic targets for BRAF(V600E) inhibitors, we used hTERT/CDK4R24C/p53DD-immortalized primary human melanocytes genetically modified to ectopically express BRAF(V600E) or NRAS(G12D) and observed induction of the AP-1 transcription factor family member c-Jun. Using a dominant negative approach, in vitro cell proliferation assays, western blots, and flow cytometry showed that MAPK signaling via BRAF(V600E) promotes melanoma cell proliferation at G1 through AP-1-mediated negative regulation of the INK4 family member, cyclin-dependent kinase inhibitor 2C (CDKN2C), and the CIP/KIP family member, cyclin-dependent kinase inhibitor 1A (CDKN1A). These effects were antagonized by pharmacological inhibition of CDKN2C and CDKN1A targets CDK2 and CDK4 in vitro. In contrast to BRAF(V600E) or NRAS(G12D)-expressing melanocytes, melanoma cells have an inherent resistance to suppression of AP-1 activity by BRAF(V600E)- or MEK-inhibitors. Here, CDK2/4 inhibition statistically significantly augmented the effects of BRAF(V600E)- or MEK-inhibitors on melanoma cell viability in vitro and growth in athymic nude Foxn1(nu) mice (P .03 when mean tumor volume at day 13 was compared for BRAF(V600E) inhibitor vs BRAF(V600E) inhibitor plus CDK2/4 inhibition; P .02 when mean tumor volume was compared for MEK inhibitor vs MEK inhibitor plus CDK2/4 inhibition; P values were calculated by a two-sided Welch t test; n 48 mice per group). C1 [Jalili, Ahmad; Wagner, Christine; Pathria, Gaurav; Mertz, Kirsten D.; Stingl, Georg; Wagner, Stephan N.] Med Univ Vienna, Div Immunol Allergy & Infect Dis, Dept Dermatol, A-1090 Vienna, Austria. [Wagner, Stephan N.] Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1010 Vienna, Austria. [Pashenkov, Mikhail] Fed Med & Biol Agcy, Natl Res Ctr, Inst Immunol, Clin Immunol Lab, Moscow, Russia. [Widlund, Hans R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Widlund, Hans R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Widlund, Hans R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Lupien, Mathieu] Dartmouth Med Sch, Dept Genet, Norris Cotton Canc Ctr, Lebanon, NH USA. [Brunet, Jean-Philippe; Golub, Todd R.; Ramaswamy, Sridhar] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Brunet, Jean-Philippe; Golub, Todd R.; Ramaswamy, Sridhar] MIT, Cambridge, MA 02139 USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Dana Farber Canc Inst, Ctr Genome Discovery, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Fisher, David E.] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Melanoma Program Med Oncol, Boston, MA 02115 USA. [Ramaswamy, Sridhar] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Ramaswamy, Sridhar] Harvard Stem Cell Inst, Cambridge, MA USA. RP Wagner, SN (reprint author), Med Univ Vienna, Div Immunol Allergy & Infect Dis, Dept Dermatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM stephan.wagner@meduniwien.ac.at OI Wagner, Stephan/0000-0003-4941-7029 FU FWF-Austrian Science Fund [L590-B12]; Austrian Society of Dermatology and Venerology FX The research was supported by the FWF-Austrian Science Fund (L590-B12 to SNW) and by a grant from the Austrian Society of Dermatology and Venerology (to AJ). NR 31 TC 14 Z9 14 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV PY 2012 VL 104 IS 21 BP 1673 EP 1679 DI 10.1093/jnci/djs373 PG 7 WC Oncology SC Oncology GA 035SS UT WOS:000310969600010 PM 22997239 ER PT J AU Yoo, JW Nakagawa, S Kim, S AF Yoo, Ji Won Nakagawa, Shunichi Kim, Sulgi TI Effect of Reimbursement Reductions on Bone Mineral Density Testing for Female Medicare Beneficiaries SO JOURNAL OF WOMENS HEALTH LA English DT Article ID X-RAY ABSORPTIOMETRY; OSTEOPOROSIS SCREENING GUIDELINES; UNITED-STATES; CARE; TRENDS; ADHERENCE; SETTINGS; ACCESS; ADULTS; DXA AB Background: We examined whether the recent reimbursement reductions on the bone mineral density (BMD) test affected BMD testing in female Medicare beneficiaries with or without supplemental private health insurance. Methods: Retrospectively analyzing hospital administrative and clinical data on female Medicare beneficiaries (n = 1320), we reviewed whether participants received BMD testing before (January 2004-December 2006) or after (January 2007-December 2009) reimbursement reductions for BMD testing. After adjusting for demographics and clinical characteristics, we performed Cox proportional hazard regression analyses of the BMD test including data from all study participants; we then performed separate regression analyses using data with or without supplemental private health insurance. Results: In those without supplemental private health insurance (n = 421), less frequent BMD testing occurred after reimbursement reductions for BMD testing (hazard ratio [HR] 0.67, 95% confidence intervals [CI] 0.34-0.98; p = 0.03). By contrast, in the overall participants (n = 1320) and those with supplemental private health insurance (n = 899), the number of BMD tests did not change significantly after reimbursement reductions for BMD testing. Conclusions: We found a significant association between reimbursement reductions and decrease in BMD tests in female Medicare beneficiaries without supplemental private health insurance. C1 [Yoo, Ji Won] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Yoo, Ji Won] Vet Affairs Ann Arbor Healthcare Syst, Geriatr Res Educ & Clin Ctr, Ann Arbor, MI USA. [Nakagawa, Shunichi] Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. [Nakagawa, Shunichi] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Kim, Sulgi] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Yoo, JW (reprint author), Univ Michigan, Sch Med, Dept Internal Med, 300 N Ingalls Bldg,Room 932, Ann Arbor, MI 48109 USA. EM yoojiw@trinity-health.org FU American Geriatrics Society Seed Grant Research Program FX This project was supported by the American Geriatrics Society Seed Grant Research Program. The funding source had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. We thank Pil Park, Ph.D. (University of Michigan Medical School), and Daehyun Kim, M.D., M.P.H. (Harvard Medical School), for their valuable feedback on study design, analysis interpretation, and manuscript preparation. NR 25 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2012 VL 21 IS 11 BP 1144 EP 1148 DI 10.1089/jwh.2012.3517 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 034BI UT WOS:000310844700007 PM 22966834 ER PT J AU Blood, EA Ullrich, NJ Hirshfeld-Becker, DR Seely, EW Connelly, MT Warfield, CA Emans, SJ AF Blood, Emily A. Ullrich, Nicole J. Hirshfeld-Becker, Dina R. Seely, Ellen W. Connelly, Maureen T. Warfield, Carol A. Emans, S. Jean TI Academic Women Faculty: Are They Finding the Mentoring They Need? SO JOURNAL OF WOMENS HEALTH LA English DT Article ID US MEDICAL-SCHOOLS; GENDER-DIFFERENCES; CAREER; ADVANCEMENT; OUTCOMES; PROGRAM; IMPACT; WORK; LIFE AB Background: Although women comprise an increasing proportion of US medical school faculty, they are underrepresented at higher ranks. Lack of effective mentoring may contribute to this disparity. We examined the role of academic rank, research focus, parenting, and part-time work on mentoring importance, needs, and gaps. Methods: In 2009, women faculty members of Harvard Medical School and Harvard School of Dental Medicine were invited by e-mail to participate in a 28-item structured questionnaire. Descriptive statistics and adjusted logistic regressions were used to identify relevant themes. Results: Of the 1179 women faculty who responded, 54% had a mentor, and 72% without a mentor desired mentoring. The most important mentor characteristic identified was availability. Respondents endorsed most mentoring areas as important (range 51%-99%); 52% of respondents identified mentoring gaps (area important and unmet) in developing and achieving career goals and negotiation skills. Interest in mentorship for skills needed for advancement (research and lecturing skills and getting national recognition) was significantly associated with lower rank. Assistant professors were most likely to identify mentoring related to writing and publishing articles, whereas associate professors identified program development/strategic planning as important. Faculty who are parents identified gaps in finding collaborators and balancing work and family life. Conclusions: This survey identified a desire for both comprehensive and targeted mentoring to address gaps that varied by faculty rank, research focus, parenting, and work time status. Strategies to enhance mentoring should address career stages and include a structured framework for assessing mentoring gaps. C1 [Blood, Emily A.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA 02115 USA. [Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Blood, Emily A.; Emans, S. Jean] Boston Childrens Hosp, Div Adolescent Med, Boston, MA 02115 USA. [Emans, S. Jean] Boston Childrens Hosp, Off Fac Dev, Boston, MA 02115 USA. [Hirshfeld-Becker, Dina R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Seely, Ellen W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Connelly, Maureen T.] Harvard Univ, Sch Med, Off Fac Affairs, Boston, MA USA. [Connelly, Maureen T.] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Warfield, Carol A.] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. RP Blood, EA (reprint author), Boston Childrens Hosp, Clin Res Ctr, 300 Longwood Ave, Boston, MA 02115 USA. EM Emily.blood@childrens.harvard.edu OI Emans, S. Jean/0000-0002-4535-7850 NR 23 TC 11 Z9 11 U1 2 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2012 VL 21 IS 11 BP 1201 EP 1208 DI 10.1089/jwh.2012.3529 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 034BI UT WOS:000310844700014 PM 22906003 ER PT J AU Shinagare, AB Okajima, Y Oxnard, GR DiPiro, PJ Johnson, BE Hatabu, H Nishino, M AF Shinagare, Atul B. Okajima, Yuka Oxnard, Geoffrey R. DiPiro, Pamela J. Johnson, Bruce E. Hatabu, Hiroto Nishino, Mizuki TI Unsuspected pulmonary embolism in lung cancer patients: Comparison of clinical characteristics and outcome with suspected pulmonary embolism SO LUNG CANCER LA English DT Article DE Lung cancer; Pulmonary embolism; Venous thromboembolism ID VENOUS THROMBOEMBOLIC DISEASE; ONCOLOGY PATIENTS; RISK; THROMBOSIS; CT; PREVENTION; FREQUENCY; SURVIVAL; COHORT; TUMORS AB Purpose: Compare the clinical characteristics, rate of recurrent venous thromboembolism (VTE) and outcome of suspected and unsuspected pulmonary embolism (PE) detected on computed tomography in patients with lung cancer. Methods: In this IRB-approved retrospective study, 77 patients [38 men, 39 women; mean age 64 (range, 35-90)] with lung cancer who developed PE between January 2004 and December 2009 were identified using research patient data registry and medical records. Patients with suspected (45/77, 58%) and unsuspected (32/77, 42%) PE were compared for the characteristics, treatment of PE, and rate of recurrent VTE using Fisher's exact test. The survival was compared using log-rank test, and Cox proportional hazards regression models were applied for univariate and multivariable analyses. Results: Most cases of PE were found in patients undergoing chemotherapy (79%) and with metastatic disease (70%). Suspected PE more commonly involved main/lobar pulmonary arteries (33/45, 73% vs. 9/32, 28%), while unsuspected PE more frequently involved of segmental/subsegmental arteries (p = 0.0001). All 11 cases of squamous cell carcinoma had suspected PE. Suspected and unsuspected PE did not differ in terms of age, gender, presence of metastatic disease at the time of PE or treatment for PE. 44/45 (98%) patients with suspected PE and 30/32 (94%) patients with unsuspected PE were treated for PE, mostly with anticoagulation (68/74, 92%). Recurrent VTE was seen in 20% (9/45) of suspected PE and 19% (6/32) of unsuspected PE (p = 1.00). Median survival after PE was 5.6 months in suspected group and 6.2 month in unsuspected group, without significant difference by univariate or multivariate analyses. Conclusion: Although unsuspected PE more frequently involved peripheral pulmonary arteries, the treatments of PE, bleeding complications, rates of recurrent VTE, and survival after PE were similar for clinically suspected and unsuspected PE. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Shinagare, Atul B.; DiPiro, Pamela J.; Nishino, Mizuki] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Shinagare, Atul B.; Okajima, Yuka; DiPiro, Pamela J.; Hatabu, Hiroto; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Oxnard, Geoffrey R.; Johnson, Bruce E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Nishino, M (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM Mizuki_Nishino@dfci.harvard.edu FU NCI [1K23CA157631]; National Institutes of Health [1RO1CA114465-01, 5R21 CA11627-02]; National Cancer Institute Specialized Program of Research Excellence in Lung Cancer [2P50CA090578-06]; Genentech Inc.; Doris and William Krupp Research Fund in Thoracic Oncology; American Society of Clinical Oncology Translational Research Professorship FX The investigators were supported by 2009-11 Agfa Health Care/RSNA Research Scholar Grant and 1K23CA157631 (NCI) (M.N.), Grants 1RO1CA114465-01 (B.E.J.) and 5R21 CA11627-02 (H.H.) from the National Institutes of Health. Grant No. 2P50CA090578-06 (B.E.J.) from the National Cancer Institute Specialized Program of Research Excellence in Lung Cancer, and a grant from Genentech Inc., as well as by the Doris and William Krupp Research Fund in Thoracic Oncology and American Society of Clinical Oncology Translational Research Professorship. NR 28 TC 17 Z9 19 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD NOV PY 2012 VL 78 IS 2 BP 161 EP 166 DI 10.1016/j.lungcan.2012.08.007 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 035JZ UT WOS:000310944000007 PM 22959241 ER PT J AU Villar, J Kacmarek, RM AF Villar, J. Kacmarek, R. M. TI The American-European Consensus Conference definition of the acute respiratory distress syndrome is dead, long live positive end-expiratory pressure! SO MEDICINA INTENSIVA LA English DT Article DE Acute respiratory distress syndrome; Positive end-expiratory pressure; Standard ventilatory settings; American-European Consensus Conference; PaO2/FiO(2) ratio ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; CLINICAL-TRIAL; GAS-EXCHANGE; FAILURE; MORTALITY; OUTCOMES; ARDS AB In 1994, an American-European Consensus Conference (AECC) formalized the criteria for the diagnosis of the acute respiratory distress syndrome (ARDS). Although that definition is simple to apply in the clinical setting, it has been challenged over the years in several studies since the assessment of the oxygenation defect does not require standardized ventilatory support. We were the first to propose new guidelines, based on a specific, standard method of evaluating oxygenation status, a proposal that was later advocated by others. To address the limitations of the AECC definition, a modified ARDS definition has been proposed by a task force panel of experts, referred to as the Berlin Defintion, using a terminology similar to that we previously proposed. However, that proposal has several methodological flaws. Since all ARDS patients start off with terrible oxygenation, the Berlin Definition offers no room for stratifying and identifyng true ARDS patients since there is no further re-evaluation of the hypoxemia under standard ventilator setting in a specific time period. In this Point of View, we review the history of the definition of ARDS and discussed the methodological concerns regarding adopting this new, revised ARDS definition. (C) 2012 Elsevier Espana, S.L. and SEMICYUC. All rights reserved. C1 [Villar, J.] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, J.] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. [Kacmarek, R. M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, R. M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III, Spain [PI 10/0393]; Asociacion Cientifica Putmon y Ventilacion Mecanica FX Supported by Instituto de Salud Carlos III, Spain (PI 10/0393) and the Asociacion Cientifica Putmon y Ventilacion Mecanica. NR 22 TC 5 Z9 7 U1 0 U2 8 PU ELSEVIER DOYMA SL PI BARCELONA PA TRAVESERA DE GARCIA, 17-21, BARCELONA, 08021, SPAIN SN 0210-5691 J9 MED INTENSIVA JI Med. Intensiv. PD NOV PY 2012 VL 36 IS 8 BP 571 EP 575 DI 10.1016/j.medin.2012.08.010 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 035FY UT WOS:000310930000008 PM 23017630 ER PT J AU Nishino, M Klepeis, VE Yeap, BY Bergethon, K Morales-Oyarvide, V Dias-Santagata, D Yagi, Y Mark, EJ Iafrate, AJ Mino-Kenudson, M AF Nishino, Michiya Klepeis, Veronica E. Yeap, Beow Y. Bergethon, Kristin Morales-Oyarvide, Vicente Dias-Santagata, Dora Yagi, Yukako Mark, Eugene J. Iafrate, A. John Mino-Kenudson, Mari TI Histologic and cytomorphologic features of ALK-rearranged lung adenocarcinomas SO MODERN PATHOLOGY LA English DT Article DE ALK; cytopathology; hepatoid cells; lung adenocarcinoma; signet ring cells; small biopsy ID ANAPLASTIC LYMPHOMA KINASE; EML4-ALK FUSION GENE; PROGNOSTIC-SIGNIFICANCE; MICROPAPILLARY PATTERN; CANCER; INHIBITOR; MUTATIONS; TUMORS; EGFR AB Chromosomal rearrangements leading to constitutive activation of anaplastic lymphoma receptor tyrosine kinase (ALK) define a category of lung adenocarcinomas that may be amenable to targeted therapy with the ALK inhibitor crizotinib. Defining distinctive features of ALK-rearranged (ALK+) lung adenocarcinomas may help identify cases that merit molecular testing. However, data describing the morphologic features of ALK+ lung adenocarcinomas are conflicting and are primarily based on analysis of resected primary lung tumors. It is unclear whether the findings from prior studies are applicable to metastatic lung tumors or to small biopsy/cytology specimens. To address these issues, we examined resection, excision, small biopsy, and cytology cell block specimens from 104 ALK+ and 215 ALK- lung adenocarcinomas from primary and metastatic sites. All cases were evaluated for ALK rearrangements by fluorescence in situ hybridization. The predominant histologic subtypes and distinctive cytomorphologic features were assessed in each case. Primary ALK+ lung adenocarcinomas showed a significant association with solid, micropapillary, and papillary-predominant histologic patterns and tumor cells with a signet ring or hepatoid cytomorphology. Among metastatic lung tumors and small biopsy/cytology specimens, the only distinguishing morphologic feature of ALK+ tumors was the presence of signet ring cells. Based on these results, we developed a morphology-based scoring system for predicting ALK rearrangements in lung adenocarcinomas. The scoring system predicted ALK rearrangements in a new cohort of 78 lung adenocarcinomas (29 ALK+ and 49 ALK-) with a sensitivity of 88% and a specificity of 45%. In conclusion, ALK+ lung adenocarcinomas have distinctive morphologic features, with signet ring cells showing a significant association with ALK rearrangements irrespective of tumor site (primary vs metastatic) or specimen type. However, morphologic screening alone will not detect a minority of ALK+ lung adenocarcinomas, and the routine use of ancillary studies may be warranted to identify all patients who may benefit from crizotinib treatment. Modern Pathology (2012) 25, 1462-1472; doi: 10.1038/modpathol.2012.109; published online 29 June 2012 C1 [Nishino, Michiya; Klepeis, Veronica E.; Bergethon, Kristin; Morales-Oyarvide, Vicente; Dias-Santagata, Dora; Yagi, Yukako; Mark, Eugene J.; Iafrate, A. John; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Nishino, Michiya; Klepeis, Veronica E.; Yeap, Beow Y.; Bergethon, Kristin; Morales-Oyarvide, Vicente; Dias-Santagata, Dora; Yagi, Yukako; Mark, Eugene J.; Iafrate, A. John; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 122, Boston, MA 02114 USA. EM mminokenudson@partners.org NR 32 TC 45 Z9 45 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 2012 VL 25 IS 11 BP 1462 EP 1472 DI 10.1038/modpathol.2012.109 PG 11 WC Pathology SC Pathology GA 033KR UT WOS:000310795400004 PM 22743652 ER PT J AU van der Ploeg, AT Barohn, R Carlson, L Charrow, J Clemens, PR Hopkin, RJ Kishnani, PS Laforet, P Morgan, C Nations, S Pestronk, A Plotkin, H Rosenbloom, BE Sims, KB Tsao, E AF van der Ploeg, Ans T. Barohn, Richard Carlson, Lisa Charrow, Joel Clemens, Paula R. Hopkin, Robert J. Kishnani, Priya S. Laforet, Pascal Morgan, Claire Nations, Sharon Pestronk, Alan Plotkin, Horacio Rosenbloom, Barry E. Sims, Katherine B. Tsao, Elisa TI Open-label extension study following the Late-Onset Treatment Study (LOTS) of alglucosidase alfa SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Genetics; Inherited metabolic disease; Glycogenoses; Neuromuscular disease; Pompe disease ID POMPE-DISEASE AB Objective: Late-onset Pompe disease is a progressive, debilitating, and often fatal neuromuscular disorder resulting from the deficiency of a lysosomal enzyme, acid alpha-glucosidase. This extension study was conducted to determine the durability of the efficacy and safety of alglucosidase alfa observed over a period of 78 weeks in the Late-Onset Treatment Study (LOTS). Methods: Patients who completed the LOTS study were eligible for this open-label extension study and received alglucosidase alfa 20 mg/kg biweekly for an additional 26 weeks. The primary efficacy assessments were the distance walked during a 6-minute walk test and the percentage of predicted forced vital capacity in the upright position. Data are reported as change from patient's original LOTS baseline for each measure. Results: The benefit of alglucosidase alfa treatment observed in LOTS at Week 78 was, in general, maintained at Week 104. The mean increase in distance walked measured 28.2 +/- 66.5 m from LOTS baseline to Week 78 and 21.3 +/- 78.0 m from LOTS baseline to Week 104. The mean change from baseline in percentage of predicted forced vital capacity was 1.3%+/- 5.7% from LOTS baseline to Week 78 and 0.8%+/- 6.7% from LOTS baseline to Week 104. Treatment-related adverse events were mainly infusion-associated reactions observed in 35% of patients. No deaths or anaphylactic reactions were observed during the extension study. Conclusions: The LOTS Extension study showed that patients treated with alglucosidase alfa for up to 104 weeks maintained the improved walking distance and stabilization in pulmonary function observed in the first 78 weeks of alglucosidase alfa therapy. (C) 2012 Elsevier Inc. All rights reserved. C1 [van der Ploeg, Ans T.] Erasmus MC Univ Med Ctr, Univ Hosp, Sophia Childrens Hosp,Div Metab Dis & Genet, Ctr Lysosomal & Metab Dis,Dept Pediat, NL-3015 GJ Rotterdam, Netherlands. [Barohn, Richard] Univ Kansas, Dept Neurol, Kansas City, MO USA. [Carlson, Lisa; Morgan, Claire; Plotkin, Horacio; Tsao, Elisa] Genzyme Corp, Boston, MA USA. [Charrow, Joel] Childrens Mem Hosp, Div Genet Birth Defects & Metab, Chicago, IL 60614 USA. [Clemens, Paula R.] Univ Pittsburgh, Dept Vet Affairs Med Ctr, Neurol Serv, Pittsburgh, PA USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Kishnani, Priya S.] Duke Univ, Med Ctr, Div Chief, Durham, NC USA. [Laforet, Pascal] Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France. [Nations, Sharon] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Pestronk, Alan] Washington Univ, Sch Med, St Louis, MO USA. [Sims, Katherine B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Clemens, Paula R.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. RP van der Ploeg, AT (reprint author), Erasmus MC Univ Med Ctr, Univ Hosp, Sophia Childrens Hosp,Div Metab Dis & Genet, Ctr Lysosomal & Metab Dis,Dept Pediat, Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM a.vanderploeg@erasmusmc.nl; rbarohn@kumc.edu; lisa.carlson@genzyme.com; jcharrow@northwestern.edu; clempr@upmc.edu; rob.hopkin@cchmc.org; priya.kishnani@duke.edu; pascal.laforet@psl.aphp.fr; claire.morgan@genzyme.com; Sharon.Nations@UTSouthwestern.edu; pestronka@neuro.wustl.edu; hplotkin@gmail.com; rosenbloomb@toweroncology.com; sims@helix.mgh.harvard.edu; elisa.tsao@genzyme.com OI Hopkin, Robert/0000-0003-0770-5516 FU Genzyme, a Sanofi company FX This study was sponsored by Genzyme, a Sanofi company. All of the authors contributed to this article by drafting/revising the manuscript for content. The authors take full responsibility for the contents of this paper, which do not represent the views of the Department of Veterans Affairs or the United States Government. NR 12 TC 27 Z9 29 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD NOV PY 2012 VL 107 IS 3 BP 456 EP 461 DI 10.1016/j.ymgme.2012.09.015 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 032LM UT WOS:000310720200030 PM 23031366 ER PT J AU Lovejoy, TI Dobscha, SK Cavanagh, R Turk, DC Morasco, BJ AF Lovejoy, Travis I. Dobscha, Steven K. Cavanagh, Renee Turk, Dennis C. Morasco, Benjamin J. TI Chronic Pain Treatment and Health Service Utilization of Veterans with Hepatitis C Virus Infection SO PAIN MEDICINE LA English DT Article DE Hepatitis C; Chronic Pain; Veterans; Health Service Utilization ID UNITED-STATES; PRIMARY-CARE; METHADONE-MAINTENANCE; PSYCHIATRIC-DISORDERS; ADMINISTRATIVE DATA; SUBSTANCE USE; PREVALENCE; POPULATION; COMPLEMENTARY; COMORBIDITY AB Objectives. Hepatitis C virus (HCV) infection is estimated to affect 2% of the general U.S. population and chronic pain is a common comorbidity among persons with HCV. The primary purpose of this study was to compare health service utilization of U.S. military veterans with HCV with and without the presence of comorbid chronic pain. Design. Cross-sectional study with retrospective review of patient medical records. Patients. One hundred seventy-one U.S. military veterans with confirmed HCV, recruited through a single U.S. Veterans Administration hospital. Outcome Measures. Medical service utilization data from the past 5 years were extracted from participants' electronic medical records. Results. Sixty-four percent of veterans with HCV (N = 110) had chronic pain. Veterans with HCV and chronic pain utilized more health services including total inpatient stays (odds ratio [OR] = 2.58 [1.46, 4.56]) and days hospitalized for psychiatric services (OR = 5.50 [3.37, 8.99]), compared to participants with HCV and no chronic pain, after statistically adjusting for demographic, psychiatric, substance use, medical comorbidity, and disability covariates. In addition, those with HCV and chronic pain had more total outpatient visits with primary care providers (OR = 1.73 [1.15, 2.59]), physical therapists (OR = 9.57 [4.79, 19.11]), and occupational therapists (OR = 2.72 [1.00, 7.48]). Conclusions. Patients with HCV and chronic pain utilize medical services to a greater extent than patients with HCV but no chronic pain. Future studies that examine the efficacy of both pharmacological and nonpharmacological pain treatment for patients with comorbid HCV and chronic pain appear warranted. C1 [Lovejoy, Travis I.; Dobscha, Steven K.; Morasco, Benjamin J.] Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, Portland, OR 97239 USA. [Dobscha, Steven K.; Morasco, Benjamin J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97239 USA. [Cavanagh, Renee] Univ Pacific, Sch Profess Psychol, Hillsboro, OR USA. [Cavanagh, Renee] Portland VA Res Fdn, Portland, OR USA. [Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. RP Lovejoy, TI (reprint author), Portland VA Med Ctr, Mental Hlth & Clin Neurosci Div, P3MHDC,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM travis.lovejoy@va.gov FU United States National Institute on Drug Abuse [K23DA023467] FX No author reports having any financial or other potential conflict of interest with this study. This study was supported in part by award K23DA023467 from the United States National Institute on Drug Abuse to Dr. Morasco. NR 46 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV PY 2012 VL 13 IS 11 BP 1407 EP 1416 DI 10.1111/j.1526-4637.2012.01476.x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 036TQ UT WOS:000311055000005 PM 22958315 ER PT J AU Sehn, F Chachamovich, E Vidor, LP Dall-Agnol, L de Souza, ICC Torres, ILS Fregni, F Caumo, W AF Sehn, Francislea Chachamovich, Eduardo Vidor, Liliane Pinto Dall-Agnol, Letizzia Custodio de Souza, Izabel C. Torres, Iraci L. S. Fregni, Felipe Caumo, Wolnei TI Cross-Cultural Adaptation and Validation of the Brazilian Portuguese Version of the Pain Catastrophizing Scale SO PAIN MEDICINE LA English DT Article DE Chronic Pain; Catastrophizing; Brazilian Pain Catastrophizing Scale ID HEALTH-STATUS; PSYCHOLOGICAL DISTRESS; COPING STRATEGIES; GENDER; FIT; VALIDITY; MODEL; RELIABILITY; POPULATION; DISABILITY AB Objective. Catastrophizing is a maladaptive response to pain and is one of the factors that contribute to the chronicity of some pain syndromes. The Pain Catastrophizing Scale (PCS) assists both treatment planning and outcome assessment. Its use is limited in Portuguese-speaking countries because of the lack of a validated translated version. We conducted the validation of the Brazilian Portuguese (BP)-PCS and explored its psychometric properties. This study reports the internal consistency, factor structure, and its capability to discriminate pain reported by patients with specific chronic pain conditions. Methods. Three hundred eighty-four patients, 317 women (82.55%), aged 1879 years with chronic nonmalignant pain attending an outpatient multidisciplinary pain center participated in this cross-sectional study. The instruments were the BP-PCS, pain intensity, pain interference in functional capacity, and a sociodemographic questionnaire. One subsample with chronic tensional headache (CTH) according to the criteria of the International Headache Society (N = 19), and another with a diagnosis of fibromyalgia according to the American College of Rheumatology criteria (N = 50) were selected to assess the discriminative properties of BP-PCS. Results. We observed good internal consistency (Cronbach's a values of 0.91 for the total BP-PCS, and 0.93 [helplessness], 0.88 [magnification], and 0.86 [rumination] for the respective subdomains). The item-total correlation coefficients ranged from 0.91 to 0.94. Confirmatory factor analysis (CFA) supported the three factors structure, with the comparative fit index = 0.98, root mean square error of approximation = 0.09, and normed fit index = 0.98. Significant correlations were found for pain intensity, pain interference, and patient's mood (correlation coefficients ranged from 0.48 to 0.66, P < 0.01). No significant gender difference was observed for BP-PCS scores. When comparing scores of BP-PCS scale and subscales between the selected control group (patients with pain scores on visual analog scale equal or lower than 40 mm in the most part of the day in the last 6 months) and patients with fibromyalgia or CTH, we observed lower scores for the former group. Conclusion. Our findings support the validity and reliability of the BP-PCS. The scale showed satisfactory psychometric properties. CFA provides support for the three-factor structure reported in previous studies. This factor structure presented good discriminative properties to identify catastrophizers who present with mild chronic pain, fibromyalgia, and CTH. The BP-PCS is a valuable tool for use in scientific studies and in the clinical setting in patients with chronic pain in Brazilian Portuguese-speaking countries. C1 [Custodio de Souza, Izabel C.; Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Lab Pain & Neuromodulat, HCPA, BR-90035003 Porto Alegre, RS, Brazil. [Sehn, Francislea; Vidor, Liliane Pinto; Dall-Agnol, Letizzia; Custodio de Souza, Izabel C.; Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Sch Med, BR-90035003 Porto Alegre, RS, Brazil. [Sehn, Francislea; Vidor, Liliane Pinto; Dall-Agnol, Letizzia; Torres, Iraci L. S.; Caumo, Wolnei] Univ Fed Rio Grande do Sul, Pain & Palliat Care Serv, HCPA, BR-90035003 Porto Alegre, RS, Brazil. [Caumo, Wolnei] Univ Fed Rio Grande do Sul, Dept Pharmacol, Inst Ciencias Basicas Saude, BR-90035003 Porto Alegre, RS, Brazil. [Chachamovich, Eduardo] McGill Univ, Dept Psychiat, Montreal, PQ, Canada. [Caumo, Wolnei] Spaulding Rehabil Hosp, Lab Neuromodulat, Dept Phys Med & Rehabil, Boston, MA USA. [Caumo, Wolnei] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fregni, Felipe] Harvard Univ, Sch Med, Boston, MA USA. RP Caumo, W (reprint author), Univ Fed Rio Grande do Sul, Lab Pain & Neuromodulat, HCPA, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. EM caumo@cpovo.net RI Torres, iraci/G-6693-2012 OI Torres, iraci/0000-0002-3081-115X FU Committee for the Development of Higher Education Personnel-CAPES-PNPD/CAPES; National Council for Scientific and Technological Development-CNPq; Postgraduate Program in Medical Sciences at the School of Medicine of the Federal University of Rio Grande do Sul; Postgraduate Research Group at the Hospital de Clinicas de Porto Alegre; Foundation of Support of Research at Rio Grande do Sul (FAPERGS) FX This research was supported by grants from the following Brazilian agencies: Committee for the Development of Higher Education Personnel-CAPES-PNPD/CAPES (for W. C and I. C. C. S), National Council for Scientific and Technological Development-CNPq (Dr. I. L. S. Torres, Dr. W. Caumo); Postgraduate Program in Medical Sciences at the School of Medicine of the Federal University of Rio Grande do Sul, Postgraduate Research Group at the Hospital de Clinicas de Porto Alegre, and Foundation of Support of Research at Rio Grande do Sul (FAPERGS). We would like to express our appreciation to Professor Michael Sullivan for his permission to use the PCS questionnaire. NR 38 TC 21 Z9 21 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV PY 2012 VL 13 IS 11 BP 1425 EP 1435 DI 10.1111/j.1526-4637.2012.01492.x PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 036TQ UT WOS:000311055000007 PM 23036076 ER PT J AU Kissane, NA Itani, KMF AF Kissane, Nicole A. Itani, Kamal M. F. TI A Decade of Ventral Incisional Hernia Repairs with Biologic Acellular Dermal Matrix: What Have We Learned? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ABDOMINAL-WALL RECONSTRUCTION; SMALL-INTESTINAL SUBMUCOSA; SHORT-TERM OUTCOMES; COLLAGEN IMPLANT; CADAVERIC DERMIS; FOLLOW-UP; DEFECTS; MANAGEMENT; CLOSURE; MESH AB Background: Innovative types of biologic mesh have provided new alternatives to ventral incisional hernia repair, especially in the face of contamination. The authors studied the experience and outcomes of patients who underwent repair of a ventral incisional hernia with biologic mesh. Methods: Online database and detailed reference searches were conducted. Studies chosen for review had a sample size of at least 40 patients, level IV evidence at most, and a Methodological Index for Nonrandomized Studies index of at least 10. Indications for use of biologic mesh, type of mesh, patient comorbidities, and surgical techniques were also noted. Results: Eight studies fulfilled the search criteria and included 635 patients using AlloDerm, Surgisis, and Strattice biologic tissue matrices. In one study, indications and surgical techniques were standardized, and follow-up was prospective. In the other seven studies, indications, surgical techniques, and follow-up were assessed retrospectively. The mean patient age, when reported, was 55.7 years. Body mass index ranged from 30 to 35 kg/m(2) in 44 percent of the reported patients. In seven of the eight studies [565 patients (89 percent)], the mean follow-up was 25.8 months and the mean hernia recurrence rate was 21 percent. Complication rate exceeded 20 percent in most studies. Conclusions: Biologic tissue matrices are mostly used in contaminated fields, which has allowed for a one-stage repair with no or little subsequent mesh removal. Ventral incisional hernia repair with these matrices continues to be plagued by a high recurrence rate and complications. Prospective randomized trials are needed to properly direct practice in the use of these meshes and evaluate their ultimate value. (Plast. Reconstr. Surg. 130 (Suppl. 2): 194S, 2012.) C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Vet Affairs Boston Healthcare Syst, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, Surg Serv 112A, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM kitani@va.gov FU LifeCell Corporation FX Dr. Itani has received research support from LifeCell Corporation. The authors have no competing financial interests to declare. NR 72 TC 32 Z9 32 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 2012 VL 130 IS 5 SU 2 BP 194S EP 202S DI 10.1097/PRS.0b013e318265a5ec PG 9 WC Surgery SC Surgery GA 034BJ UT WOS:000310844800027 PM 23096971 ER PT J AU Hoerster, KD Jakupcak, M McFall, M Unutzer, J Nelson, KM AF Hoerster, Katherine D. Jakupcak, Matthew McFall, Miles Unuetzer, Juergen Nelson, Karin M. TI Mental health and somatic symptom severity are associated with reduced physical activity among US Iraq and Afghanistan veterans SO PREVENTIVE MEDICINE LA English DT Article DE Veterans; Exercise; Depression ID FREEDOM VETERANS; RISK-FACTORS; SAMPLE; CARE; DEPRESSION; DIAGNOSES; VALIDITY; OBESITY AB Objective. Ensuring that Iraq and Afghanistan veterans engage in adequate physical activity is essential to prevent metabolic and cardiovascular diseases, and promote psychological well-being. Identifying factors associated with physical activity in this population will yield areas for targeted interventions aimed at increasing activity. Method. Correlates of meeting physical activity recommendations (>= 150 min/week of moderate-to-vigorous physical activity [MVPA]) were examined in Iraq/Afghanistan veterans assessed at intake to VA Puget Sound Healthcare System's post-deployment health clinic (May, 2005-August, 2009; N=266). Results. The majority were male (94.3%) and Caucasian (70.7%), with an average age of 29.8 (SD=7.3) years. Participants engaged in a median of 180 weekly MVPA minutes. Among those meeting (59%) and not meeting (41%) recommendations, median weekly MVPA minutes were 540 and 0, respectively. In multivariate regression models, higher levels of depression (p=.042) and somatic (p=.018) symptom severity were associated with significantly decreased odds of meeting physical activity recommendations. Conclusion. Overall, physical activity engagement among Iraq/Afghanistan veteran VA patients was above the level specified in national recommendations. Those with higher depressive and somatic symptoms were less likely to meet physical activity recommendations and may benefit from targeted physical activity promotion interventions. Published by Elsevier Inc. C1 [Hoerster, Katherine D.; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Seattle Div, Res & Dev Serv, Seattle, WA 98108 USA. [Hoerster, Katherine D.; Jakupcak, Matthew; McFall, Miles; Unuetzer, Juergen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Jakupcak, Matthew; McFall, Miles] VA Puget Sound Healthcare Syst, Seattle Div, Mental Hlth Serv, Seattle, WA 98108 USA. [Unuetzer, Juergen] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [Nelson, Karin M.] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA 98108 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Hoerster, KD (reprint author), 1660 S Columbian Way,S-116, Seattle, WA 98108 USA. EM Katherine.Hoerster@va.gov; Matthew.Jakupcak@va.gov; Miles.McFall@va.gov; unutzer@u.washington.edu; Karin.Nelson@va.gov FU VA Puget Sound Healthcare System FX This material is the result of work supported by resources from VA Puget Sound Healthcare System. NR 21 TC 6 Z9 6 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 2012 VL 55 IS 5 BP 450 EP 452 DI 10.1016/j.ypmed.2012.08.017 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 036VT UT WOS:000311061100020 PM 22959890 ER PT J AU John, LK Loewenstein, G Volpp, KG AF John, Leslie K. Loewenstein, George Volpp, Kevin G. TI Empirical observations on longer-term use of incentives for weight loss SO PREVENTIVE MEDICINE LA English DT Article DE Weight loss; Obesity; Behavioral economics; Intervention ID CHOICE; HEALTH; RISK AB Behavioral economic-based interventions are emerging as powerful tools to help individuals accomplish their own goals, including weight loss. Deposit contract incentive systems give participants the opportunity to put their money down toward losing weight, which they forfeit if they fail to lose weight; lottery incentive systems enable participants to win money if they attain weight loss goals. In this paper, we pool data from two prior studies to examine a variety of issues that unpublished data from those studies allow us to address. First, examining data from the deposit contract treatments in greater depth, we investigate factors affecting deposit frequency and size, and discuss possible ways of increasing deposits. Next, we compare the effectiveness of both deposit contract and lottery interventions as a function of participant demographic characteristics. These observations may help to guide the design of future, longer-term, behavioral economic-based interventions. (C) 2012 Elsevier Inc. All rights reserved. C1 [John, Leslie K.] Harvard Univ, Sch Business, Mkt Unit, Boston, MA 02163 USA. [Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Loewenstein, George] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Volpp, Kevin G.] Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA USA. [Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn Wharton Sch, Dept Hlth Care Management, Philadelphia, PA USA. RP John, LK (reprint author), Harvard Univ, Sch Business, Mkt Unit, Morgan Hall 169, Boston, MA 02163 USA. EM ljohn@hbs.edu NR 19 TC 10 Z9 10 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV 1 PY 2012 VL 55 SU 1 BP S68 EP S74 DI 10.1016/j.ypmed.2012.01.022 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 036VV UT WOS:000311061300011 PM 22342291 ER PT J AU Park, JD Mitra, N Asch, DA AF Park, James D. Mitra, Nandita Asch, David A. TI Public opinion about financial incentives for smoking cessation SO PREVENTIVE MEDICINE LA English DT Article DE Financial incentive; Tobacco cessation; Public opinion ID HEALTH LOCUS; REINFORCEMENT; SMOKERS AB Objective. The aim of this study is to assess public support for a smoking cessation policy involving financial incentives. Methods. We conducted a randomized controlled trial using an experimental survey design. One of four questionnaire versions was distributed to participants. Each version described a smoking cessation treatment costing $750 per success, including an unspecified treatment, medication, or financial incentive paid to the smoker. Participants indicated whether they would support a $25 increase in their annual health insurance premium to pay for the treatment. Questionnaires were distributed to adults waiting at public transportation depots in Philadelphia between May and August 2010. Results. 1010 individuals completed the questionnaires about willingness to support the policy: 53% female, 27% African-American, 18% current smokers, and 46% with a household income below $40,000. The response rate was greater than 50%. Overall support for all smoking cessation treatments was 41.6%. The financial incentive version received the lowest support (393%) but that support did not statistically differ from the treatment (45.8%, p=0.14) or medication (41.7%, p=0.58) versions. Conclusions. Financial incentives were perceived no differently than currently used medications for smoking cessation. Most participants did not support any smoking cessation treatment options. (C) 2012 Elsevier Inc. All rights reserved, C1 [Park, James D.; Asch, David A.] Univ Penn, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr Res 9E, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Mitra, Nandita; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Colonial Penn Ctr, Philadelphia, PA 19104 USA. RP Park, JD (reprint author), Univ Penn, Div Gen Internal Med, 1005 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jdpark@mail.med.upenn.edu; nanditam@mail.med.upenn.edu; asch@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU VAL Health; Center for Public Health Initiatives, University of Pennsylvania; [T32-HP-10026-17] FX David Asch received consulting fees from VAL Health. No other conflicts of interest are reported.; Funding/support: T32-HP-10026-17 and the Center for Public Health Initiatives, University of Pennsylvania. The funding sources did not have any role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 18 TC 10 Z9 10 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV 1 PY 2012 VL 55 SU 1 BP S41 EP S45 DI 10.1016/j.ypmed.2012.06.013 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 036VV UT WOS:000311061300007 PM 22735040 ER PT J AU Schmidt, H Asch, DA Halpern, SD AF Schmidt, Harald Asch, David A. Halpern, Scott D. TI Fairness and wellness incentives: What is the relevance of the process-outcome distinction? SO PREVENTIVE MEDICINE LA English DT Article DE Wellness incentives; Prevention; Fairness; Discrimination; Patient Protection and Affordable Care Act ID FINANCIAL INCENTIVES; SMOKING-CESSATION; PERSONAL RESPONSIBILITY; SOCIAL DETERMINANTS; IMPROVE HEALTH; CONTROLLED-TRIAL; WEIGHT-LOSS; POLICY; CARE; PREFERENCES AB Objective. To determine whether the commonly drawn distinction between the fairness of incentives targeting behavioral processes (or effort) and those targeting outcomes (or achievement) provide suitable grounds for favoring either approach in healthcare research, policy and practice. Methods. Conceptual analysis, literature review. Results. A categorical distinction between process- and outcome-based incentives is less crisp than it seems. Both processes and outcomes involve targets, and both are subject to differences - across and within socio-economic groups - in circumstance and perspective. Thus, a spectrum view is more appropriate, in which the fairness of incentive programs increases with the extent of control that people have. The effectiveness of incentives is a further relevant consideration, and some available evidence suggests that incentives closer to the outcome-end of the spectrum can be more effective. Conclusions. Simple distinctions between processes and outcomes by themselves provide little assurance that programs are effective or fair. Effectiveness can and should be assessed empirically. Assessments of fairness should focus on the extent to which an activity or outcome might be feasible and under an individual's control, not on whether it targets a process or outcome. Rigid uniform targets for all are generally less desirable than those that reward person-specific improvement. (C) 2012 Elsevier Inc. All rights reserved. C1 [Schmidt, Harald; Asch, David A.; Halpern, Scott D.] Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA. [Asch, David A.] VA Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. [Halpern, Scott D.] Univ Penn, Med Ctr, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. RP Schmidt, H (reprint author), Univ Penn, Leonard Davis Inst, Ctr Hlth Incent & Behav Econ, Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM schmidth@mail.med.upenn.edu; asch@wharton.upenn.edu; shalpern@exchange.upenn.edu OI Asch, David/0000-0002-7970-286X NR 53 TC 9 Z9 9 U1 0 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 EI 1096-0260 J9 PREV MED JI Prev. Med. PD NOV 1 PY 2012 VL 55 SU 1 BP S118 EP S123 DI 10.1016/j.ypmed.2012.03.005 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 036VV UT WOS:000311061300019 PM 22449482 ER PT J AU Tsan, JY Zeber, JE Stock, EM Sun, FF Copeland, LA AF Tsan, Jack Y. Zeber, John E. Stock, Eileen M. Sun, Fangfang Copeland, Laurel A. TI Primary Care Mental Health Integration and Treatment Retention Among Iraq and Afghanistan War Veterans SO PSYCHOLOGICAL SERVICES LA English DT Article DE integrated care; mental health services; primary care; posttraumatic stress disorder; veterans ID TRAUMATIC BRAIN-INJURY; POSTTRAUMATIC-STRESS-DISORDER; PSYCHIATRIC-DIAGNOSES; RETURNING VETERANS; MEDICAL-CARE; SERVICES; AFFAIRS; PTSD; ACCESS; SYSTEM AB Despite the high prevalence of posttraumatic stress disorder (PTSD) and medical comorbidity among veterans from Iraq/Afghanistan (OEF/OIF), keeping these patients engaged in health care is challenging. Primary Care Mental Health Integration (PC-MHI), an initiative in the Veterans Health Administration (VA), sought to improve access to mental health care from within primary care. This study examined the lag between first PC-MHI visit and next mental/medical care visit, if any, and the relationship of PC-MHI with short-term (subsequent year) and long-term (4 years later) use of VA. We identified 2,470 OEF/OIF veterans receiving care during fiscal year 2006 (FY06) in a regional VA health care system. Unconditional survival analysis modeled time to next mental/medical visit and logistic regression modeled short- and long-term care as a function of PC-MHI, demo-graphics, and clinical covariates. Of 181 patients in the PC-MHI program, 60%/ 18% returned for mental/medical care within 1 month, and 82%/74% within 1 year. Sixty-one percent (1,503) were still using the VA in FY09. Short-term mental care was related to prior-year PC-MHI. Consistent correlates of short- and long-term mental/medical care included physical comorbidity and Priority 1 status. Most patients attended mental health appointments subsequent to PC-MHI, and PC-MHI was correlated with mental health treatment retention in adjusted models for our cohort. Need for treatment, notably VA Priority 1 status and physical comorbidity, were the primary correlates of care-seeking. Developing innovative approaches to engaging new veterans in care remains imperative as multiple options will be necessary to meet the needs of these complex patients. C1 [Tsan, Jack Y.] US Dept Vet Affairs, VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX 76711 USA. [Tsan, Jack Y.] Texas A&M Hlth Sci Ctr, Houston, TX USA. RP Tsan, JY (reprint author), US Dept Vet Affairs, VISN 17 Ctr Excellence Res Returning War Vet, 4800 Mem Dr 151C, Waco, TX 76711 USA. EM Jack.Tsan@va.gov OI Copeland, Laurel/0000-0002-9478-0209 NR 44 TC 8 Z9 8 U1 1 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 EI 1939-148X J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2012 VL 9 IS 4 SI SI BP 336 EP 348 DI 10.1037/a0028308 PG 13 WC Psychology, Clinical SC Psychology GA 036ZP UT WOS:000311071100002 PM 22545824 ER PT J AU Gates, MA Holowka, DW Vasterling, JJ Keane, TM Marx, BP Rosen, RC AF Gates, Margaret A. Holowka, Darren W. Vasterling, Jennifer J. Keane, Terence M. Marx, Brian P. Rosen, Raymond C. TI Posttraumatic Stress Disorder in Veterans and Military Personnel: Epidemiology, Screening, and Case Recognition SO PSYCHOLOGICAL SERVICES LA English DT Article DE epidemiology; military personnel; posttraumatic stress disorder; screening; veterans ID GULF-WAR VETERANS; MENTAL-HEALTH PROBLEMS; MALE VIETNAM VETERANS; SELF-REPORTED SYMPTOMS; COMBAT-RELATED PTSD; UK ARMED-FORCES; RISK-FACTORS; IRAQ-WAR; SEXUAL TRAUMA; PRIMARY-CARE AB Posttraumatic stress disorder (PTSD) is a psychiatric disorder that affects 7-8% of the general U.S. population at some point during their lifetime; however, the prevalence is much higher among certain subgroups, including active duty military personnel and veterans. In this article, we review the empirical literature on the epidemiology and screening of PTSD in military and veteran populations, including the availability of sensitive and reliable screening tools. Although estimates vary across studies, evidence suggests that the prevalence of PTSD in deployed U.S. military personnel may be as high as 14-16%. Prior studies have identified trauma characteristics and pre- and posttrauma factors that increase risk of PTSD among veterans and military personnel. This information may help to inform prevention and screening efforts, as screening programs could be targeted to high-risk populations. Large-scale screening efforts have recently been implemented by the U.S. Departments of Defense and Veterans Affairs. Given the prevalence and potential consequences of PTSD among veterans and active duty military personnel, development and continued evaluation of effective screening methods is an important public health need. C1 [Gates, Margaret A.; Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA 02472 USA. [Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.; Marx, Brian P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Holowka, Darren W.; Vasterling, Jennifer J.; Keane, Terence M.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Gates, MA (reprint author), New England Res Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM mgates@neriscience.com NR 157 TC 42 Z9 43 U1 8 U2 34 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2012 VL 9 IS 4 SI SI BP 361 EP 382 DI 10.1037/a0027649 PG 22 WC Psychology, Clinical SC Psychology GA 036ZP UT WOS:000311071100004 PM 23148803 ER PT J AU Baker, RR Stenger, C Gurel, L Goldstein, G AF Baker, Rodney R. Stenger, Charles Gurel, Lee Goldstein, Gerald TI Patient Care by VA Psychologists in the 1950s and 1960s SO PSYCHOLOGICAL SERVICES LA English DT Article DE health care of veterans; history of VA psychology; history of psychology AB In 1946, the Veterans Administration, now the Department of Veterans Affairs (VA), underwent extensive organizational and professional changes to accommodate the health care needs of veterans returning from World War Two. In addition to an introduction and brief history of these changes, three psychologists who began their careers in the VA in the first years after that reorganization discuss their patient care experiences, both as trainees and as staff psychologists. C1 [Baker, Rodney R.; Stenger, Charles; Gurel, Lee] US Dept Vet Affairs, Washington, DC USA. [Goldstein, Gerald] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Baker, RR (reprint author), 10710 Old Blue Lane, San Antonio, TX 78230 USA. EM rodbaker@att.net NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1541-1559 J9 PSYCHOL SERV JI Psychol. Serv. PD NOV PY 2012 VL 9 IS 4 SI SI BP 417 EP 426 DI 10.1037/a0029515 PG 10 WC Psychology, Clinical SC Psychology GA 036ZP UT WOS:000311071100008 PM 22844985 ER PT J AU Constans, JI Vasterling, JJ Deitch, E Han, XT Tharp, ALT Davis, TD Sullivan, G AF Constans, Joseph I. Vasterling, Jennifer J. Deitch, Elizabeth Han, Xiaotong Tharp, Andra L. Teten Davis, Teri D. Sullivan, Greer TI Pre-Katrina Mental Illness, Postdisaster Negative Cognitions, and PTSD Symptoms in Male Veterans Following Hurricane Katrina SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE trauma; posttraumatic stress disorder; negative cognitions ID POSTTRAUMATIC-STRESS-DISORDER; PERCEIVED SOCIAL SUPPORT; INVENTORY PTCI; APPRAISALS; DEPRESSION; EXPOSURE; MODEL; RISK AB Although negative cognitions following traumatic experiences have been studied in persons with posttraumatic stress disorder (PTSD), very little of this work has been conducted in the context of disasters or with individuals with preexisting mental illness. The current study was designed to examine whether negative cognitions would be associated with increased post-Katrina PTSD symptom severity and whether pre-Katrina mental illness would be associated with increased negative cognitions in response to Hurricane Katrina. Data from a sample of 503 Gulf Coast area male veterans who responded to a telephone survey administered approximately 21/2 years after Hurricane Katrina were used to examine the study hypotheses. As predicted, negative cognitions were strongly associated with PTSD symptom severity, and individuals with pre-Katrina mental illness did show higher levels of post-Katrina negative cognitions. The strong relationship between negative cognitions and PTSD symptom severity persisted even after removing variance associated with Katrina-related stress exposures, level of perceived social support, and physical damage to property. An interaction between post-Katrina cognitive bias and pre-Katrina mental illness was also observed, showing that cognitive bias was a slightly stronger associate of PTSD symptom severity for individuals without preexisting PTSD. Nevertheless, cognitive bias still showed a strong relationship with PTSD for those with pre-Katrina mental illness, and a mediation analysis indicated that negative cognitions partially mediated the relationship between previous mental illness and PTSD severity. C1 [Constans, Joseph I.] SE Louisiana Vet Hlth Care Syst, New Orleans, LA USA. [Constans, Joseph I.] Tulane Univ, New Orleans, LA 70118 USA. [Vasterling, Jennifer J.] VA Boston Healthcare Syst, Boston, MA USA. [Vasterling, Jennifer J.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Deitch, Elizabeth] Univ New Orleans, New Orleans, LA 70148 USA. [Han, Xiaotong; Sullivan, Greer] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Tharp, Andra L. Teten] Baylor Coll Med, Houston, TX 77030 USA. [Davis, Teri D.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Constans, JI (reprint author), SLVHCS, POB 61011, New Orleans, LA 70161 USA. EM joseph.constans@va.gov NR 28 TC 6 Z9 6 U1 2 U2 20 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD NOV PY 2012 VL 4 IS 6 BP 568 EP 577 DI 10.1037/a0027487 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 036YR UT WOS:000311068700003 ER PT J AU Mott, JM Graham, DP Teng, EJ AF Mott, Juliette M. Graham, David P. Teng, Ellen J. TI Perceived Threat During Deployment: Risk Factors and Relation to Axis I Disorders SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE perceived threat; veterans; PTSD; Axis I diagnoses ID POSTTRAUMATIC-STRESS-DISORDER; GULF-WAR; TRAUMA; VETERANS; HEALTH; REPRESENTATIONS; INFORMATION; COMORBIDITY; DEPRESSION; EXPOSURE AB This study sought to (a) examine the relation between perceived threat during deployment and the postdeployment presence of Axis I disorders and (b) identify developmental and deployment-related variables that predict level of threat perception during deployment. Participants were 1,740 Operation Enduring Freedom or Operation Iraqi Freedom veterans who completed the Deployment Risk and Resilience Inventory during a postdeployment screening at a large Veterans Affairs hospital. Greater perceived threat during deployment was significantly associated with the postdeployment presence of posttraumatic stress disorder, anxiety disorders, and mood disorders, but not substance use disorders. Perceived threat was also positively associated with the presence of comorbid Axis I diagnoses. Results of a multiple regression analysis indicated that, after controlling for combat exposure, deployment environment and deployment preparation significantly predicted perceived threat during deployment. These findings indicate that veterans' reports of perceived threat during deployment are associated with a wide variety of mental health disorders and suggest that efforts to increase deployment preparation and facilitate adjustment to the deployment environment have the potential to temper troops' threat appraisals. C1 [Mott, Juliette M.; Graham, David P.; Teng, Ellen J.] Michael E DeBakey VA Med Ctr, Minneapolis, MN USA. [Mott, Juliette M.; Graham, David P.; Teng, Ellen J.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Mott, JM (reprint author), Dept Vet Affairs Med Ctr, Mental Hlth Care Line Trauma Recovery Program 116, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM Juliette.Mott@va.gov RI Graham, David /J-1158-2014 NR 28 TC 7 Z9 7 U1 1 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD NOV PY 2012 VL 4 IS 6 BP 587 EP 595 DI 10.1037/a0025778 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 036YR UT WOS:000311068700006 ER PT J AU Lee, AF Li, NC Lamade, R Schuler, A Prentky, RA AF Lee, Austin F. Li, Nien-Chen Lamade, Raina Schuler, Ann Prentky, Robert A. TI PREDICTING HANDS-ON CHILD SEXUAL OFFENSES AMONG POSSESSORS OF INTERNET CHILD PORNOGRAPHY SO PSYCHOLOGY PUBLIC POLICY AND LAW LA English DT Article DE child pornography; child molesters; Internet offenders; risk ID OFFENDERS; METAANALYSIS; RECIDIVISM; PEDOPHILIA; SAMPLE AB The recent Supreme Court ruling in U.S. v. Comstock (2010) upheld the constitutionality of The Adam Walsh Act, which provides for civil commitment of child pornography (CP) offenders certified as sexually dangerous, thereby approving litigation of all such prisoners in the federal system. The two studies reported here sought to address the question: What is the likelihood that an individual convicted of child pornography offenses has a prior history of a hands-on sexual offense involving a child or has a high probability of committing such an offense? Our sample consisted of 349 participants: 113 who committed an Internet sexual offense only and no other known or self-reported hands-on sexual offense, 176 child molesters who reported no Internet sexual offense, and 60 child molesters that reported committing an Internet sexual offense. Study 1 yielded two scales, one reflecting Antisocial Behavior (AB) and one reflecting Internet Preoccupation (IP). Those two scales predicted membership in the combined sample of child molesters with a high degree of accuracy (c = 0.75). Study two revealed that all three groups were discrete with respect to AB and IP. By increasing the IP scale by 1 point, the odds of being an IO rather than a CM increased by 86%. The plotted conditional probabilities increased linearly as values on the AB scale increase, from 0.27 when AB = 0 to 0.84 when AB = 13. Our results are discussed in terms of risk discrimination among possessors of child pornography, relevance of risk to the statutory third prong element of serious difficulty, and the policy implications of the findings reported here. C1 [Lee, Austin F.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Li, Nien-Chen] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. [Lamade, Raina; Prentky, Robert A.] Fairleigh Dickinson Univ, Sch Psychol, Teaneck, NJ 07666 USA. [Schuler, Ann] Justice Resource Inst, Res Dept, Boston, MA USA. RP Prentky, RA (reprint author), Fairleigh Dickinson Univ, Sch Psychol T WH1 01, 1000 River Rd, Teaneck, NJ 07666 USA. EM rprentky@fdu.edu NR 32 TC 5 Z9 5 U1 1 U2 24 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1076-8971 J9 PSYCHOL PUBLIC POL L JI Psychol. Public Policy Law PD NOV PY 2012 VL 18 IS 4 BP 644 EP 672 DI 10.1037/a0027517 PG 29 WC Health Policy & Services; Law; Psychology, Multidisciplinary SC Health Care Sciences & Services; Government & Law; Psychology GA 036VR UT WOS:000311060900005 ER PT J AU Scheinfeld, MH Shifteh, K Avery, LL Dym, H Dym, RJ AF Scheinfeld, Meir H. Shifteh, Keivan Avery, Laura L. Dym, Harry Dym, R. Joshua TI Teeth: What Radiologists Should Know SO RADIOGRAPHICS LA English DT Article ID MAXILLARY SINUS; PERIAPICAL LESIONS; ODONTOGENIC ORIGIN; DENTAL-CARIES; HISTOLOGICAL-FINDINGS; RADIOPAQUE LAMINA; 3RD MOLAR; CT SCANS; TOMOGRAPHY; INFECTIONS AB Disease of the teeth and their support structures is common and frequently seen at imaging of the head and neck. Recognition of dental disease by the interpreting radiologist has the potential to alter the course of patient care, such as when periapical disease is identified as the cause of sinusitis or pericoronitis is identified as the cause of deep neck infection. Furthermore, incidental recognition of carious lesions in both children and adults who are undergoing CT for other reasons may alert the patient and care team of the need for a dental consultation. In fact, most of the images of dental and periodontal conditions that are used in this article were obtained from CT studies that were performed to investigate other problems. Familiarity with the imaging appearance of common dental conditions, such as hyperdontia and hypodontia, tooth trauma, periodontal disease, caries, periapical disease, odontogenic sinusitis, and deep neck infections, allows the radiologist to render a timely, confident, and specific diagnosis of dental abnormalities, even when such findings are unexpected. (C) RSNA, 2012 . radiographics.rsna.org C1 [Scheinfeld, Meir H.; Dym, R. Joshua] Montefiore Med Ctr, Dept Radiol, Div Emergency Radiol, Bronx, NY 10467 USA. [Shifteh, Keivan] Montefiore Med Ctr, Div Neuroradiol, Dept Radiol, Bronx, NY 10467 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. [Dym, Harry] Brooklyn Hosp Ctr, Dept Dent & Maxillofacial Surg, Brooklyn, NY USA. RP Scheinfeld, MH (reprint author), Montefiore Med Ctr, Dept Radiol, Div Emergency Radiol, 111 E 210th St, Bronx, NY 10467 USA. EM mscheinf@montefiore.org OI Scheinfeld, Meir H/0000-0001-8880-4318 NR 85 TC 7 Z9 7 U1 0 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2012 VL 32 IS 7 BP 1927 EP 1944 DI 10.1148/rg.327125717 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 036MT UT WOS:000311031100011 PM 23150849 ER PT J AU Shah, SH Nagymanyoki, Z Ramaiya, NH Howard, S AF Shah, Shaan H. Nagymanyoki, Zoltan Ramaiya, Nikhil H. Howard, Stephanie TI AIRP Best Cases in Radiologic-Pathologic Correlation Coal Workers' Pneumoconiosis SO RADIOGRAPHICS LA English DT Editorial Material ID OCCUPATIONAL LUNG-DISEASE; HIGH-RESOLUTION CT; UNITED-STATES C1 [Shah, Shaan H.; Ramaiya, Nikhil H.; Howard, Stephanie] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Nagymanyoki, Zoltan] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ramaiya, Nikhil H.; Howard, Stephanie] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Shah, SH (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM Sshah18@partners.org NR 19 TC 0 Z9 0 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2012 VL 32 IS 7 BP 2047 EP 2052 DI 10.1148/rg.327115137 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 036MT UT WOS:000311031100021 PM 23150857 ER PT J AU Kaafarani, HMA Hawn, MT Itani, KMF AF Kaafarani, Haytham M. A. Hawn, Mary T. Itani, Kamal M. F. TI Individual surgical decision-making and comparative effectiveness research SO SURGERY LA English DT Article ID CRITICALLY-ILL PATIENTS; CLINICAL-TRIALS C1 [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA 02132 USA. [Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [Kaafarani, Haytham M. A.; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Hawn, Mary T.] Vet Affairs Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Hawn, Mary T.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy,VABHCS 112, W Roxbury, MA 02132 USA. EM kitani@va.gov NR 13 TC 1 Z9 1 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2012 VL 152 IS 5 BP 787 EP 789 DI 10.1016/j.surg.2012.03.023 PG 3 WC Surgery SC Surgery GA 035JY UT WOS:000310943900001 PM 22657726 ER PT J AU Turner, TH Horner, MD VanKirk, KK Myrick, H Tuerk, PW AF Turner, Travis H. Horner, Michael D. VanKirk, Kathryn K. Myrick, Hugh Tuerk, Peter W. TI A Pilot Trial of Neuropsychological Evaluations Conducted via Telemedicine in the Veterans Health Administration SO TELEMEDICINE AND E-HEALTH LA English DT Article DE military medicine; telepsychiatry; telemedicine ID TRAUMATIC BRAIN-INJURY; SERVICES; RELIABILITY; DEMENTIA; TELEHEALTH; PROVISION; DISORDER; MEMORY; AREAS AB Introduction: Many veterans live in rural areas distant from Veterans Affairs Medical Centers (VAMCs) and receive primary medical care from community-based outpatient clinics (CBOCs). These veterans often must travel great distances to the nearest VAMC for neuropsychological evaluations, resulting in poor access to care, travel reimbursement costs, fee-basis evaluations of uncontrolled quality, and driving safety concerns. Return trips for feedback compound complications. Accordingly, we initiated a pilot trial of neuropsychological evaluation and feedback via telemedicine (i.e., clinical videoconferencing). Subjects and Methods: Participants were veterans referred for neuropsychological evaluation from a rural CBOC 115 miles from the regional VAMC. All veterans were given the choice to undergo evaluation at the CBOC via telemedicine or in-person at the VAMC. Telemedicine equipment allowed presentation of digitized material with simultaneous patient observation. Testing materials were organized in numbered folders and given to veterans by CBOC clerks immediately prior to evaluation. Clerks returned completed materials via facsimile. Results: Fifteen veterans from the rural CBOC were seen for neuropsychological evaluation. Eight chose telemedicine evaluation. Groups based on evaluation modality appeared similar on demographics, referral basis, resulting neuropsychiatric diagnoses, and follow-through on recommendations. No significant technical or clinical difficulties were encountered, and veterans reported satisfaction with telemedicine. All veterans requested feedback via telemedicine. Conclusions: Neuropsychological evaluation via telemedicine is feasible and appears comparable to in-person evaluation. Experiences are encouraging and consistent with the broader literature on the acceptance of and satisfaction with clinical videoconferencing. Future studies will assess possible psychometric issues in clinical populations. C1 [Turner, Travis H.; Horner, Michael D.; VanKirk, Kathryn K.; Myrick, Hugh; Tuerk, Peter W.] Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv Line, Charleston, SC USA. [Turner, Travis H.; Horner, Michael D.; VanKirk, Kathryn K.; Myrick, Hugh; Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Turner, Travis H.] Med Univ S Carolina, Div Neurol, Dept Neurosci, Charleston, SC 29425 USA. RP Turner, TH (reprint author), Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv Line, 109 Bee St,MH 116, Charleston, SC 29401 USA. EM turnertr@musc.edu NR 44 TC 7 Z9 7 U1 3 U2 13 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED E-HEALTH JI Telemed. e-Health PD NOV PY 2012 VL 18 IS 9 BP 662 EP 667 DI 10.1089/tmj.2011.0272 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 034BX UT WOS:000310846200002 PM 23050802 ER PT J AU Brooks-Worrell, B Narla, R Palmer, JP AF Brooks-Worrell, Barbara Narla, Radhika Palmer, Jerry P. TI Biomarkers and immune-modulating therapies for Type 2 diabetes SO TRENDS IN IMMUNOLOGY LA English DT Review DE immunotherapy; type 2 diabetes; immunomodulatory drugs; obesity; biomarkers; autoimmunity; inflammation ID ADIPOSE-TISSUE INFLAMMATION; C-REACTIVE PROTEIN; ACTIVATED RECEPTOR-GAMMA; NECROSIS-FACTOR-ALPHA; PANCREATIC BETA-CELL; REGULATORY T-CELLS; INSULIN-RESISTANCE; METABOLIC DISEASE; PPAR-GAMMA; HISTONE DEACETYLASES AB Recent advances in understanding the etiology of obesity, metabolic syndrome, and type 2 diabetes (T2D) have established involvement of the immune system. These developments highlight the potential of immunomodulatory therapies for treatment of these conditions. Here, we discuss current and new immunotherapeutic strategies for the treatment of T2D, the need for stratification of patients based on immune and autoimmune status, and biomarkers for evaluating treatment efficiency. The time has come to re-evaluate the clinical management of T2D patients using metabolic parameters alone, and to realize that patients should be stratified based on their immune and/or autoimmune status prior to initiation of therapy to realize fully the potential of immunomodulatory strategies for T2D. C1 [Brooks-Worrell, Barbara; Palmer, Jerry P.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. [Brooks-Worrell, Barbara; Narla, Radhika; Palmer, Jerry P.] VA Puget Sound Hlth Care Syst, Dept Hosp & Specialty Med, Seattle, WA 98108 USA. [Narla, Radhika] Univ Washington, Dept Gen Internal Med, Seattle, WA 98108 USA. RP Brooks-Worrell, B (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. EM bbrooks@u.washington.edu NR 91 TC 14 Z9 15 U1 2 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2012 VL 33 IS 11 BP 546 EP 553 DI 10.1016/j.it.2012.07.002 PG 8 WC Immunology SC Immunology GA 039PP UT WOS:000311259300003 PM 22897868 ER PT J AU Deshpande, AJ Bradner, J Armstrong, SA AF Deshpande, Aniruddha J. Bradner, James Armstrong, Scott A. TI Chromatin modifications as therapeutic targets in MLL-rearranged leukemia SO TRENDS IN IMMUNOLOGY LA English DT Review DE chromatin modifications; leukemia; epigenetics; targeted therapy; MLL ID MIXED-LINEAGE LEUKEMIA; RNA-POLYMERASE-II; BROMODOMAIN PROTEIN BRD4; FUSION PROTEINS; STEM-CELLS; HISTONE H3; TRANSCRIPTIONAL ELONGATION; SET DOMAIN; P-TEFB; MLL-AF9-INDUCED LEUKEMOGENESIS AB MLL-rearranged leukemias exemplify malignancies with perturbations of the epigenetic landscape. Specific chromatin modifications that aid in the perpetuation of MLL fusion gene driven oncogenic programs are being defined, presenting novel avenues for therapeutic intervention. Proof-of-concept studies have recently been reported, using small-molecule inhibitors targeting the histone methyltransferase disruptor of telomeric silencing 1-like (DOT1L), or the acetyl-histone binding protein bromodomain containing protein 4 (BRD4) showing potent activity against MLL-rearranged leukemias in preclinical models. It is apparent that intensive efforts will be made toward the further development of small-molecule inhibitors targeting these, and other chromatin-associated protein targets. These studies may lead to the advent of a new generation of much-needed therapeutic modalities in leukemia and other cancers. C1 [Deshpande, Aniruddha J.; Armstrong, Scott A.] Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. [Bradner, James] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Bradner, James] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Armstrong, Scott A.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Armstrong, SA (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02215 USA. EM scott.armstrong@childrens.harvard.edu FU American Cancer Society; Leukemia and Lymphoma Society; Gabrielle's Angel Foundation; National Cancer Institute [U01CA105423, R01CA140575] FX We would like to apologize to our colleagues in the field whose work may not have been cited owing to space considerations. We would like to acknowledge support from the American Cancer Society, the Leukemia and Lymphoma Society, Gabrielle's Angel Foundation and the National Cancer Institute (U01CA105423, R01CA140575) to S.A.A. A.J.D. is supported by the NCI Howard Temin K99 Award. S.A.A. is a consultant for Epizyme Inc. NR 92 TC 31 Z9 31 U1 0 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD NOV PY 2012 VL 33 IS 11 BP 563 EP 570 DI 10.1016/j.it.2012.06.002 PG 8 WC Immunology SC Immunology GA 039PP UT WOS:000311259300005 PM 22867873 ER PT J AU Mao, JR AF Mao, Jianren TI Current challenges in translational pain research SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID NEUROPATHIC PAIN; THERAPEUTIC TARGETS; DRUG DEVELOPMENT; CLINICAL-TRIALS; NERVE INJURY; MODELS; SENSITIVITY; EFFICACY; CHANNELS; RATS AB The current gap between basic science research and the development of new analgesics presents a serious challenge for the future of pain medicine. This challenge is particularly difficult in the search for better treatment for comorbid chronic pain conditions because: (i) animal 'pain' models do not simulate multidimensional clinical pain conditions; (ii) animal behavioral testing does not assess subjective pain experience; (iii) preclinical data provide little assurance regarding the direction of new analgesic development; and (iv) clinical trials routinely use over-sanitized study populations and fail to capture the multidisciplinary consequences of comorbid chronic pain. Therefore, a paradigm shift in translational pain research is necessary to transform the current strategy from focusing on molecular switches of nociception to studying pain as a system-based integral response that includes psychosocial comorbidities. Several key issues of translational pain research are discussed in this review. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA 02114 USA. EM jmao@partners.org FU NIH [RO1 DA22576, RO1 DE18214, P20 DA26002] FX This work was supported by NIH grants RO1 DA22576, RO1 DE18214, and P20 DA26002. NR 75 TC 37 Z9 37 U1 0 U2 28 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 2012 VL 33 IS 11 BP 568 EP 573 DI 10.1016/j.tips.2012.08.001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 038LT UT WOS:000311176900003 PM 22959652 ER PT J AU Chao, TE Burdic, M Ganjawalla, K Derbew, M Keshian, C Meara, J McQueen, K AF Chao, Tiffany E. Burdic, MacKenzie Ganjawalla, Karan Derbew, Miliard Keshian, Christopher Meara, John McQueen, Kelly TI Survey of Surgery and Anesthesia Infrastructure in Ethiopia SO WORLD JOURNAL OF SURGERY LA English DT Article ID DEVELOPING-COUNTRIES; HOSPITALS; UGANDA; HEALTH AB Information regarding surgical capacity in the developing world is limited by the paucity of available data regarding surgical care, infrastructure, and human resources in the literature. The purpose of this study was to assess surgical and anesthesia infrastructure and human resources in Ethiopia as part of a larger study by the Harvard Humanitarian Initiative examining surgical and anesthesia capacity in ten low-income countries in Africa. A comprehensive survey tool developed by the Harvard Humanitarian Initiative was used to assess surgical capacity of hospitals in Ethiopia. A total of 20 hospitals were surveyed through convenience sampling. Eight areas of surgical and anesthesia care were examined, including access and availability, access to human resources, infrastructure, outcomes, operating room information and procedures, equipment, nongovernmental organization delivery of surgical services, and pharmaceuticals. Results were obtained over a 1-month period during October 2011. There is wide variation in accessibility, with hospital-to-population ratios ranging from 1:99,010 to 1:1,082,761. The overall physician to population ratio ranges from 1:4715 to 1:107,602. The average hospital has one to two operating rooms, 4.2 surgeons, one gynecologist, and 4.5 anesthesia providers-although in all but three hospitals anesthesiology was provided by nonphysician personnel only (i.e., a nurse anesthetist). Access to continuous electricity, running water, essential medications, and monitoring systems is very limited in all hospitals surveyed, although such access did vary across regions. This survey of Ethiopia's hospital resources attempts to identify specific areas of need where resources, education, and development can be targeted. Because the major surgical mortality comes from late presentations, increasing accessibility through infrastructure development would likely provide a major improvement in surgical morbidity and mortality rates. Infrastructure limitations of electricity, water, oxygen, and blood banking do not prove to be significant barriers to surgical care. The increasing number of physicians is promising, although efforts should be directed specifically toward increasing the number of anesthesiologists and surgeons in the country. C1 [Chao, Tiffany E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chao, Tiffany E.; Ganjawalla, Karan; Meara, John] Harvard Univ, Sch Med, Program Global Surg & Social Change, Boston, MA USA. [Burdic, MacKenzie; McQueen, Kelly] Harvard Humanitarian Initiat, Boston, MA USA. [Derbew, Miliard] Black Lion Hosp, Addis Ababa, Ethiopia. [Keshian, Christopher] Univ Virginia, Charlottesville, VA USA. RP Chao, TE (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM tchao@partners.org FU Partners Global Health Center of Expertise; MGH International Trauma and Disaster Institute; Harvard Humanitarian Initiative; Harvard Program in Global Surgery and Social Change FX Grant support was provided by the Partners Global Health Center of Expertise, the MGH International Trauma and Disaster Institute, the Harvard Humanitarian Initiative, and the Harvard Program in Global Surgery and Social Change. NR 13 TC 19 Z9 19 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 EI 1432-2323 J9 WORLD J SURG JI World J.Surg. PD NOV PY 2012 VL 36 IS 11 BP 2545 EP 2553 DI 10.1007/s00268-012-1729-3 PG 9 WC Surgery SC Surgery GA 017AH UT WOS:000309560500001 PM 22851147 ER PT J AU Lown, BA Rodriguez, D AF Lown, Beth A. Rodriguez, Dayron TI Electronic Health Records: Can We Maximize Their Benefits and Minimize Their Risks? Reply SO ACADEMIC MEDICINE LA English DT Letter C1 [Lown, Beth A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lown, Beth A.] Mt Auburn Hosp, Cambridge, MA USA. [Rodriguez, Dayron] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lown, BA (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM blown@mah.harvard.edu NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2012 VL 87 IS 11 BP 1457 EP 1457 DI 10.1097/ACM.0b013e31826e319b PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 030OI UT WOS:000310579600009 ER PT J AU Dhaliwal, G AF Dhaliwal, Gurpreet TI Clinical Excellence: Make It a Habit SO ACADEMIC MEDICINE LA English DT Editorial Material C1 [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Dhaliwal, G (reprint author), San Francisco VA Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. EM gurpreet.dhaliwal@ucsf.edu NR 3 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2012 VL 87 IS 11 BP 1473 EP 1473 DI 10.1097/ACM.0b013e31826d68d9 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 030OI UT WOS:000310579600018 PM 23111262 ER PT J AU Nashar, K Fried, LF AF Nashar, Khaled Fried, Linda F. TI Hyperuricemia and the Progression of Chronic Kidney Disease: Is Uric Acid a Marker or an Independent Risk Factor? SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE Uric acid; CKD; Hyperuricemia; Progression ID RENAL-DISEASE; CYCLOSPORINE NEPHROPATHY; IGA NEPHROPATHY; BLOOD-PRESSURE; FOLLOW-UP; INCREASES; OUTCOMES; HYPERTENSION; ALLOPURINOL; ASSOCIATION AB Hyperuricemia is seen when kidney function declines. Whether elevated uric acid (UA) levels play a role in the initiation and progression of kidney disease is a subject of a great debate. Animal studies demonstrate that elevated UA level is a risk factor for kidney disease. In humans, the relationship between UA and kidney disease is more complicated. Cross-sectional studies show an association of hyperuricemia with the presence of CKD; however, from cross-sectional studies, one cannot determine which came first the elevated UA level or the kidney disease. UA levels are also associated with other risk factors for kidney disease, including hypertension, metabolic syndrome, and microalbuminuria, but it is not clear whether these are mediators or confounders of a relationship. Observational studies suggest a relationship of UA level with incident CKD, but studies evaluating the relationship with decline in kidney function in established CKD are conflicting. Finally, small clinical trials using allopurinol to lower UA levels provide weak, but potentially promising, evidence that lowering UA levels may retard the progression of CKD. In this article, we will review the evidence of the association of hyperuricemia and CKD. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved. C1 [Nashar, Khaled] Allegheny Gen Hosp, Div Nephrol & Hypertens, Pittsburgh, PA 15212 USA. VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. RP Nashar, K (reprint author), Allegheny Gen Hosp, Div Nephrol & Hypertens, 320 East North Ave,4th Floor, Pittsburgh, PA 15212 USA. EM Knashar@wpahs.org NR 32 TC 17 Z9 18 U1 3 U2 21 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD NOV PY 2012 VL 19 IS 6 BP 386 EP 391 DI 10.1053/j.ackd.2012.05.004 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 033TC UT WOS:000310823000006 PM 23089273 ER PT J AU Mimiaga, MJ Reisner, SL Pantalone, DW O'Cleirigh, C Mayer, KH Safren, SA AF Mimiaga, Matthew J. Reisner, Sari L. Pantalone, David W. O'Cleirigh, Conall Mayer, Kenneth H. Safren, Steven A. TI A Pilot Trial of Integrated Behavioral Activation and Sexual Risk Reduction Counseling for HIV-Uninfected Men Who Have Sex with Men Abusing Crystal Methamphetamine SO AIDS PATIENT CARE AND STDS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; CLUB DRUG-USE; ADDICTION SEVERITY INDEX; SUBSTANCE USE DISORDERS; BASE-LINE DATA; BISEXUAL MEN; CONTINGENCY MANAGEMENT; GAY MEN; DOPAMINE/SEROTONIN RELEASERS; OUTPATIENT TREATMENT AB Crystal methamphetamine use is a major driver behind high-risk sexual behavior among men who have sex with men (MSM). Prior work suggests a cycle of continued crystal methamphetamine use and high-risk sex due to loss of the ability to enjoy other activities, which appears to be a side effect of this drug. Behavioral activation (BA) is a treatment for depression that involves learning to reengage in life's activities. We evaluated a novel intervention for crystal methamphetamine abuse and high-risk sex in MSM, incorporating 10 sessions of BA with integrated HIV risk reduction counseling (RR). Forty-four subjects were screened, of whom 21 met initial entry criteria. A total of 19 participants enrolled; 16 completed an open-phase study of the intervention. Behavioral assessments were conducted at baseline, 3 months postbaseline, and 6 months postbaseline. Linear mixed effects regression models were fit to assess change over time. Mean unprotected anal intercourse (UAI) episodes decreased significantly from baseline to acute postintervention (beta = -4.86; 95% confidence interval [CI] = -7.48, -2.24; p = 0.0015) and from baseline to 6 months postbaseline (beta = -5.07; 95% CI = -7.85, -2.29; p = 0.0017; test of fixed effects chi(2) = 16.59; df = 2,13; p = 0.0002). On average, there was a significant decrease over time in the number of crystal methamphetamine episodes in the past 3 months (chi(2) = 22.43; df = 2,15; p < 0.0001), and the number of days of crystal methamphetamine use in the past 30 days (chi(2) = 9.21; df = 2,15; p = 0.010). Statistically significant reductions in depressive symptoms and poly-substance use were also maintained. Adding behavioral activation to risk reduction counseling for MSM with problematic crystal methamphetamine use may augment the potency of a risk reduction intervention for this population. Due to the small sample size and time intensive intervention, future testing in a randomized design is necessary to determine efficacy, with subsequent effectiveness testing. C1 [Mimiaga, Matthew J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mimiaga, Matthew J.] Harvard Univ, Dept Epidemiol, Sch Publ Hlth, Boston, MA 02114 USA. [Reisner, Sari L.] Harvard Univ, Dept Soc Human Dev & Hlth, Sch Publ Hlth, Boston, MA 02114 USA. [Pantalone, David W.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Mayer, Kenneth H.] Harvard Univ, Div Infect Dis, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@hsph.harvard.edu FU National Institute on Drug Abuse [R03DA023393] FX This project was supported by grant number R03DA023393 (PI: Mimiaga) from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health. These findings were partially presented at the Society of Behavioral Medicine 2010 Annual Meeting, Seattle, Washington, and at the 2010 International AIDS Society Meeting, Vienna, Austria. NR 92 TC 17 Z9 17 U1 9 U2 18 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2012 VL 26 IS 11 BP 681 EP 693 DI 10.1089/apc.2012.0216 PG 13 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 033XL UT WOS:000310834600006 PM 23030605 ER PT J AU Bishu, K Deswal, A Chen, HH LeWinter, MM Lewis, GD Semigran, MJ Borlaug, BA McNulty, S Hernandez, AF Braunwald, E Redfield, MM AF Bishu, Kalkidan Deswal, Anita Chen, Horng H. LeWinter, Martin M. Lewis, Gregory D. Semigran, Marc J. Borlaug, Barry A. McNulty, Steven Hernandez, Adrian F. Braunwald, Eugene Redfield, Margaret M. TI Biomarkers in acutely decompensated heart failure with preserved or reduced ejection fraction SO AMERICAN HEART JOURNAL LA English DT Article ID SERUM CYSTATIN-C; LEFT-VENTRICULAR DYSFUNCTION; GLOMERULAR-FILTRATION RATE; NATRIURETIC-PEPTIDE; SYSTOLIC FUNCTION; OUTCOMES; ALDOSTERONE; CREATININE; MORTALITY; REGISTRY AB Background Acute decompensated heart failure (ADHF) occurs with preserved (heart failure with preserved ejection fraction [HFpEF] >= 50%) or reduced (heart failure with reduced ejection fraction [HFrEF] <50%) ejection fraction. Natriuretic peptide (NP) levels are lower in HFpEF than HFrEF. We hypothesized that lower NP levels in HFpEF may be associated with other differences in biomarkers, specifically, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, and a biomarker that reflects collagen synthesis. Methods In this prespecified ancillary analysis of patients with ADHF enrolled in the Diuretic Optimization Strategies Evaluation study, clinical features and N-terminal pro-B-type NP, cystatin C, plasma renin activity, aldosterone, oxidative stress (uric acid), and procollagen type III N-terminal peptide were compared in HFpEF and HFrEF at enrollment and 60-day follow-up. Results Compared with HFrEF (n = 219), HFpEF (n = 81) patients were older, heavier, more commonly female, less treated with RAAS antagonists, but with similar New York Heart Association class, jugular venous pressure, and edema severity. N-terminal pro-B-type NP was lower, and systolic blood pressure and cystatin C were higher in HFpEF. Despite higher systolic blood pressure and less RAAS antagonist use in HFpEF, plasma renin activity and aldosterone levels were similar in HFpEF and HFrEF as were uric acid and procollagen type III N-terminal peptide levels. Changes in biomarker levels from enrollment to 60 days were similar between HFrEF (n = 149) and HFpEF (n = 50). Conclusion Lower NP levels in decompensated HFpEF occur in association with similar ADHF severity, more impaired vascular and renal function but similar elevation of biomarkers that reflect RAAS activation, oxidative stress, and collagen synthesis as in HFrEF. (Am Heart J 2012;164:763-770.e3.) C1 [Redfield, Margaret M.] Mayo Clin, Cardiovasc Div, Rochester, MN 55905 USA. [Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA. [LeWinter, Martin M.] Univ Vermont, Burlington, VT USA. [Lewis, Gregory D.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [McNulty, Steven; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. RP Redfield, MM (reprint author), Mayo Clin, Cardiovasc Div, 200 1st St SW, Rochester, MN 55905 USA. EM redfield.margaret@mayo.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU [HL084861]; [HL084875]; [HL084877]; [HL084889]; [HL084890]; [HL084891]; [HL084899]; [HL084904]; [HL084907]; [HL084931]; [HL07111-83]; [UL1 RR024150] FX The HFCRN is supported by grants HL084861, HL084875, HL084877, HL084889, HL084890, HL084891, HL084899, HL084904, HL084907, and HL084931. K.B. is supported by HL07111-83, whereas support for mentoring K.B. as a HFCRN Skills Development fellow is provided by HL084907 and UL1 RR024150. NR 36 TC 26 Z9 27 U1 1 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2012 VL 164 IS 5 BP 763 EP U171 DI 10.1016/j.ahj.2012.08.014 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033GV UT WOS:000310783100020 PM 23137508 ER PT J AU Bhardwaj, A Rehman, SU Mohammed, AA Gaggin, HK Barajas, L Barajas, J Moore, SA Sullivan, D Januzzi, JL AF Bhardwaj, Anju Rehman, Shafiq U. Mohammed, Asim A. Gaggin, Hanna K. Barajas, Linda Barajas, Justine Moore, Stephanie A. Sullivan, Dorothy Januzzi, James L. TI Quality of life and chronic heart failure therapy guided by natriuretic peptides: Results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study SO AMERICAN HEART JOURNAL LA English DT Article ID VENTRICULAR SYSTOLIC DYSFUNCTION; TRIAL; BNP; POPULATION; VALSARTAN; SURVIVAL; METAANALYSIS; PREFERENCES; OUTCOMES; PLACEBO AB Background Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. Methods One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values <= 1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Delta) in score assessed across study procedures and as a function of outcome. Results Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, Delta MLHFQ scores modestly correlated with Delta NT-proBNP values (rho = .234; P = .006) as did relative Delta in MLHFQ score and NT-proBNP (rho = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001). Conclusions We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.gov NCT00351390). (Am Heart J 2012;164:793-799.e1.) C1 [Bhardwaj, Anju; Rehman, Shafiq U.; Mohammed, Asim A.; Gaggin, Hanna K.; Barajas, Linda; Barajas, Justine; Moore, Stephanie A.; Sullivan, Dorothy; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org NR 26 TC 17 Z9 17 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2012 VL 164 IS 5 BP 793 EP U201 DI 10.1016/j.ahj.2012.08.015 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 033GV UT WOS:000310783100024 PM 23137512 ER PT J AU Okam, MM Mandell, E Hevelone, N Wentz, R Ross, A Abel, GA AF Okam, Maureen M. Mandell, Elyse Hevelone, Nathanael Wentz, Rachel Ross, Ainsley Abel, Gregory A. TI Comparative rates of adverse events with different formulations of intravenous iron SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CHEMOTHERAPY-INDUCED ANEMIA; CHRONIC KIDNEY-DISEASE; EVERY 3 WEEKS; DARBEPOETIN ALPHA; ORAL IRON; RANDOMIZED-TRIAL; DEXTRAN; EFFICACY; SAFETY; SUPPLEMENTATION C1 [Okam, Maureen M.; Mandell, Elyse; Wentz, Rachel; Ross, Ainsley] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Hevelone, Nathanael] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Leukemia, Boston, MA 02115 USA. RP Okam, MM (reprint author), Brigham & Womens Hosp, Div Hematol, 75 Francis St,Mid Campus 3, Boston, MA 02115 USA. EM mokam@partners.org OI Hevelone, Nathanael/0000-0003-4740-2085 NR 26 TC 21 Z9 23 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2012 VL 87 IS 11 BP E123 EP E124 DI 10.1002/ajh.23322 PG 2 WC Hematology SC Hematology GA 026BT UT WOS:000310246100003 PM 22965928 ER PT J AU Di Vizio, D Morello, M Dudley, AC Schow, PW Adam, RM Morley, S Mulholland, D Rotinen, M Hager, MH Insabato, L Moses, MA Demichelis, F Lisanti, MP Wu, H Klagsbrun, M Bhowmick, NA Rubin, MA D'Souza-Schorey, C Freeman, MR AF Di Vizio, Dolores Morello, Matteo Dudley, Andrew C. Schow, Peter W. Adam, Rosalyn M. Morley, Samantha Mulholland, David Rotinen, Mirja Hager, Martin H. Insabato, Luigi Moses, Marsha A. Demichelis, Francesca Lisanti, Michael P. Wu, Hong Klagsbrun, Michael Bhowmick, Neil A. Rubin, Mark A. D'Souza-Schorey, Crislyn Freeman, Michael R. TI Large Oncosomes in Human Prostate Cancer Tissues and in the Circulation of Mice with Metastatic Disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FATTY-ACID SYNTHASE; TUMOR PROGRESSION; CELL-MIGRATION; CAVEOLIN-1; EXPRESSION; MICROVESICLES; ACTIVATION; MECHANISMS; INVASION; GROWTH AB Oncosomes are tumor-derived microvesicles that transmit signaling complexes between cell and tissue compartments. Herein, we show that amoeboid tumor cells export large (1- to 10-mu m diameter) vesicles, derived from bulky cellular protrusions, that contain metalloproteinases, RNA, caveolin-1, and the GTPase ADP-ribosylation factor 6, and are biologically active toward tumor cells, endothelial cells, and fibroblasts. We describe methods by which large oncosomes can be selectively sorted by flow cytometry and analyzed independently of vesicles <1 mu m. Structures resembling large oncosomes were identified in the circulation of different mouse models of prostate cancer, and their abundance correlated with tumor progression. Similar large vesicles were also identified in human tumor tissues, but they were not detected in the benign compartment. They were more abundant in metastases. Our results suggest that tumor microvesicles substantially larger than exosome-sized particles can be visualized and quantified in tissues and in the circulation, and isolated and characterized using clinically adaptable methods. These findings also suggest a mechanism by which migrating tumor cells condition the tumor microenvironment and distant sites, thereby potentiating advanced disease. (Am J Pathol 2012, 181:1573-1584; http://dx.doi.org/10.1016/j.ajpath.2012.07.030) C1 [Di Vizio, Dolores; Morello, Matteo; Adam, Rosalyn M.; Morley, Samantha; Rotinen, Mirja; Hager, Martin H.; Freeman, Michael R.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Div Canc Biol & Therapeut, Los Angeles, CA 90048 USA. [Bhowmick, Neil A.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Urooncol Res Program, Los Angeles, CA 90048 USA. [Di Vizio, Dolores; Morello, Matteo; Adam, Rosalyn M.; Morley, Samantha; Hager, Martin H.; Freeman, Michael R.] Childrens Hosp, Urol Dis Res Ctr, Boston, MA 02115 USA. [Dudley, Andrew C.; Moses, Marsha A.; Klagsbrun, Michael] Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. [Di Vizio, Dolores; Morello, Matteo; Freeman, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Freeman, Michael R.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Schow, Peter W.] Flow Cytometry Core Facil, Dana Farber Canc Inst, Boston, MA USA. [Mulholland, David; Wu, Hong] Univ Calif Los Angeles, David Geffen Sch Med, Inst Mol Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. [Insabato, Luigi] Univ Naples Federico II, Dept Biomorphol & Funct Sci, Naples, Italy. [Demichelis, Francesca] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA. [Demichelis, Francesca; Rubin, Mark A.] Weill Cornell Med Coll, Inst Computat Biomed, New York, NY USA. [Demichelis, Francesca] Weill Cornell Med Coll, Inst Computat Biol, New York, NY USA. [Demichelis, Francesca] Univ Trento, Ctr Integrat Biol, Trento, Italy. [Lisanti, Michael P.] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA. [D'Souza-Schorey, Crislyn] Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. RP Di Vizio, D (reprint author), Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Div Canc Biol & Therapeut, 8700 Beverly Blvd,Davis Bldg,Suite 5069, Los Angeles, CA 90048 USA. EM dolores.divizio@childrens.harvard.edu; michael.freeman@cshs.org RI Lisanti, Michael/C-6866-2013; OI Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 FU National Cancer Institute [K99CA131472]; NIH [R01CA143777, R01DK57691]; US Army [W81XWH-08-1-0150]; American Institute for Cancer Research [PDA 09A107] FX Supported by grants from the National Cancer Institute (K99CA131472 to D.D.V.), the NIH (R01CA143777 and R01DK57691 to M.R.F.), the US Army (W81XWH-08-1-0150 to M.R.F.), and the American Institute for Cancer Research (PDA 09A107 to S.M.). NR 51 TC 58 Z9 58 U1 3 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2012 VL 181 IS 5 BP 1573 EP 1584 DI 10.1016/j.ajpath.2012.07.030 PG 12 WC Pathology SC Pathology GA 031QK UT WOS:000310656800010 PM 23022210 ER PT J AU Gukovskaya, AS Gukovsky, I AF Gukovskaya, Anna S. Gukovsky, Ilya TI Autophagy and pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Review DE macroautophagy; lysosome; cathepsin; lysosome-associated membrane protein; pancreatic acinar cell; trypsin ID CERULEIN-INDUCED PANCREATITIS; LYSOSOMAL MEMBRANE-PROTEINS; ACINAR-CELL DEATH; TRYPSINOGEN ACTIVATION; MAMMALIAN-CELLS; EARLY EVENTS; RAT-LIVER; ORGANELLAR DYSFUNCTION; ZYMOGEN ACTIVATION; IMPAIRED AUTOPHAGY AB Acute pancreatitis is an inflammatory disease of the exocrine pancreas that carries considerable morbidity and mortality; its pathophysiology remains poorly understood. Recent findings from experimental models and genetically altered mice summarized in this review reveal that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis and that one cause of autophagy impairment is defective function of lysosomes. We propose that the lysosomal/autophagic dysfunction is a key initiating event in pancreatitis and a converging point of multiple deranged pathways. There is strong evidence supporting this hypothesis. Investigation of autophagy in pancreatitis has just started, and many questions about the "upstream" mechanisms mediating the lysosomal/autophagic dysfunction and the "downstream" links to pancreatitis pathologies need to be explored. Answers to these questions should provide insight into novel molecular targets and therapeutic strategies for treatment of pancreatitis. C1 [Gukovskaya, Anna S.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Gukovskaya, Anna S.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU Department of Veterans Affairs, National Institutes of Health [R01 DK-59936, AA-19730]; Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis (National Institutes of Health) [P50 AA-11999] FX Our research is supported by the Department of Veterans Affairs, National Institutes of Health Grants R01 DK-59936 and AA-19730 and, in part, by the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis (National Institutes of Health Grant P50 AA-11999). NR 113 TC 32 Z9 36 U1 0 U2 17 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2012 VL 303 IS 9 BP G993 EP G1003 DI 10.1152/ajpgi.00122.2012 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 032HS UT WOS:000310706900001 PM 22961802 ER PT J AU Hoerster, KD Lehavot, K Simpson, T McFall, M Reiber, G Nelson, KM AF Hoerster, Katherine D. Lehavot, Keren Simpson, Tracy McFall, Miles Reiber, Gayle Nelson, Karin M. TI Health and Health Behavior Differences US Military, Veteran, and Civilian Men SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID FACTOR SURVEILLANCE SYSTEM; QUALITY-OF-LIFE; INSURANCE COVERAGE; COMBAT DEPLOYMENT; PHYSICAL-ACTIVITY; NATIONAL SAMPLE; ALCOHOL-USE; CARE; DEPRESSION; RISK AB Background: Little is known about health and health behavior differences among military service veterans, active duty service members, National Guard/Reserve members, and civilians. Several important differences were identified among U.S. women from these subpopulations; to identify areas for targeted intervention, studies comparing men from these subpopulations are needed. Purpose: To compare veteran, military, and civilian men on leading U.S. health indicators. Methods: Data were from the 2010 Behavioral Risk Factor Surveillance Survey, a U.S. population-based study. In 2011, self-reported health outcomes were compared using multivariable logistic regression across male veterans (n=53,406); active duty service members (n=2144); National Guard/Reserve service members (n=3724); and civilians (n=110,116). Results: Multivariate logistic regression results are presented. Despite better healthcare access, veterans had poorer health and functioning than civilians and National Guard/Reserve members on several indicators. Veterans also were more likely than those on active duty to report diabetes. Veterans were more likely to report current smoking and heavy alcohol consumption than National Guard/Reserve members and civilian men, and lack of exercise compared to active duty men and National Guard/Reserve members. National Guard/Reserve men had higher levels of obesity, diabetes, and cardiovascular disease (versus active duty and veterans, active duty, and civilians, respectively). Active duty men were more likely to report current smoking and heavy alcohol consumption than civilians and National Guard/Reserve members, and reported more smokeless tobacco use than civilians. Conclusions: Veterans have poorer health and health behaviors; increased prevention efforts are needed from veteran-serving organizations. Despite good health, active duty men reported unhealthy lifestyles, indicating an important area for prevention efforts. (Am J Prey Med 2012;43(5):483-489) Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Hoerster, Katherine D.; Reiber, Gayle; Nelson, Karin M.] VA Puget Sound Healthcare Syst, Res & Dev Serv, Seattle, WA USA. [Lehavot, Keren; Simpson, Tracy; McFall, Miles] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle, WA USA. [Simpson, Tracy] VA Puget Sound Healthcare Syst, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA USA. [Nelson, Karin M.] VA Puget Sound Healthcare Syst, Gen Internal Med Serv, Seattle, WA USA. [Hoerster, Katherine D.; Lehavot, Keren; Simpson, Tracy; McFall, Miles] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Reiber, Gayle] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Nelson, Karin M.] Univ Washington, Dept Med, Seattle, WA USA. RP Hoerster, KD (reprint author), 1660 S Columbian Way,S-116, Seattle, WA 98108 USA. EM Hoerster@va.gov FU VA Puget Sound Health Care System, Seattle WA FX This material is the result of work supported by resources from the VA Puget Sound Health Care System, Seattle WA. The views expressed in this article are those of the authors and do not necessarily reflect the views of the Department of Veterans Affairs. NR 37 TC 63 Z9 63 U1 8 U2 31 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2012 VL 43 IS 5 BP 483 EP 489 DI 10.1016/j.amepre.2012.07.029 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 032JI UT WOS:000310713100004 PM 23079170 ER PT J AU Drehmer, JE Ossip, DJ Rigotti, NA Nabi-Burza, E Woo, H Wasserman, RC Chang, YC Winickoff, JP AF Drehmer, Jeremy E. Ossip, Deborah J. Rigotti, Nancy A. Nabi-Burza, Emara Woo, Heide Wasserman, Richard C. Chang, Yuchiao Winickoff, Jonathan P. TI Pediatrician Interventions and Thirdhand Smoke Beliefs of Parents SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID N-NITROSAMINES; TOBACCO-SMOKE; CARCINOGENICITY; BIOCHEMISTRY AB Background: Thirdhand smoke is residual tobacco smoke contamination that remains after a cigarette is extinguished. A national study indicates that adults' belief that thirdhand smoke (THS) harms children is associated with strict household no-smoking policies. The question of whether pediatricians can influence THS beliefs has not been assessed. Purpose: To identify prevalence of THS beliefs and associated factors among smoking parents, and the association of pediatrician intervention on parent belief that THS is harmful to their children. Methods: Exit interview data were collected from 1980 parents following a pediatric office visit. Parents level of agreement or disagreement that THS can harm the health of babies and children was assessed. A multivariate logistic regression model was constructed to identify whether pediatricians' actions were independently associated with parental belief that THS can harm the health of babies and children. Data were collected from 2009 to 2011, and analyses were conducted in 2012. Results: Ninety-one percent of parents believed that THS can harm the health of babies and children. Fathers (AOR=0.59, 95% CI = 0.42, 0.84) and parents who smoked more than ten cigarettes per day (AOR=0.63, 95% CI = 0.45, 0.88) were less likely to agree with this statement. In contrast, parents who received advice (AOR = 1.60, 95% CI = 1.04, 2.45) to have a smokefree home or car or to quit smoking and parents who were referred (AOR= 3.42,95% CI = 1.18, 9.94) to a "quitline" or other cessation program were more likely to agree that THS can be harmful. Conclusions: Fathers and heavier smokers were less likely to believe that THS is harmful. However, pediatricians' actions to encourage smoking parents to quit or adopt smokefree home or car policies were associated with parental beliefs that THS harms children. Trial registration: This study is registered at NCT00664261. (Am J Prey Med 2012;43(5):533-536) (C) 2012 American Journal of Preventive Medicine C1 [Drehmer, Jeremy E.; Wasserman, Richard C.] Amer Acad Pediat, Pediat Res Off Settings, Elk Grove Village, IL USA. [Winickoff, Jonathan P.] Amer Acad Pediat, Richmond Ctr, Elk Grove Village, IL USA. [Ossip, Deborah J.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Rigotti, Nancy A.; Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Rigotti, Nancy A.; Nabi-Burza, Emara; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. [Nabi-Burza, Emara; Winickoff, Jonathan P.] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [Woo, Heide] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Wasserman, Richard C.] Univ Vermont, Dept Pediat, Burlington, VT USA. RP Winickoff, JP (reprint author), Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, 15 Floor,Suite 1542A,100 Cambridge St, Boston, MA 02114 USA. EM jwinickoff@partners.org RI Wasserman , Richard/G-3775-2015; OI Drehmer, Jeremy/0000-0002-5022-5836 FU NIH NCI [R01-CA127127]; National Institute on Drug Abuse; Agency for Healthcare Research and Quality; Flight Attendant Medical Research Institute; Pediatric Research in Office Settings (PROS) Network; HRSA MCHB [HRSA 5-UA6-10-001]; AAP FX This study was supported by the NIH NCI grant R01-CA127127 (to JPW), National Institute on Drug Abuse, and the Agency for Healthcare Research and Quality. This study was also partially supported by a grant from the Flight Attendant Medical Research Institute to the AAP Julius B. Richmond Center, and the Pediatric Research in Office Settings (PROS) Network, which receives core funding from the HRSA MCHB (HRSA 5-UA6-10-001) and the AAP. NR 11 TC 14 Z9 14 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2012 VL 43 IS 5 BP 533 EP 536 DI 10.1016/j.amepre.2012.07.020 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 032JI UT WOS:000310713100011 PM 23079177 ER PT J AU Shinagare, AB Krajewski, KM Jagannathan, JP Ramaiya, NH AF Shinagare, Atul B. Krajewski, Katherine M. Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI Genitourinary Imaging: Part 2, Role of Imaging in Medical Management of Advanced Renal Cell Carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE molecular targeted therapy; renal cell carcinoma; renal cell carcinoma subtypes; toxicity; tumor response criteria ID TARGETED THERAPIES; SOLID TUMORS; CANCER-PATIENTS; HISTOLOGIC SUBTYPES; COMPUTED-TOMOGRAPHY; RESPONSE CRITERIA; FUTURE-DIRECTIONS; MTOR INHIBITORS; SUNITINIB; BEVACIZUMAB AB OBJECTIVE. Renal cell carcinoma (RCC) comprises 80-85% of all primary renal neoplasms. Knowledge of the genetic and molecular features of RCC and the advent of molecular targeted therapy have revolutionized the treatment of RCC in the past decade. This article will review the changing role of the radiologist in the management of advanced RCC, especially in terms of the new relevance of RCC subtypes, treatment-related changes on imaging, new tumor response criteria, and commonly encountered molecular targeted therapy-related toxicities. CONCLUSION. In this era of personalized cancer treatment, imaging has assumed a central role in treatment selection and follow-up of advanced RCC. C1 [Shinagare, Atul B.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Shinagare, Atul B.; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ashinagare@partners.org NR 67 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2012 VL 199 IS 5 BP W554 EP W564 DI 10.2214/AJR.12.9233 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030TM UT WOS:000310593000004 PM 23096199 ER PT J AU Bryant, A Mhyre, JM Leffert, LR Hoban, RA Yakoob, MY Bateman, BT AF Bryant, Allison Mhyre, Jill M. Leffert, Lisa R. Hoban, Rebecca A. Yakoob, Mohammad Y. Bateman, Brian T. TI The Association of Maternal Race and Ethnicity and the Risk of Postpartum Hemorrhage SO ANESTHESIA AND ANALGESIA LA English DT Article ID HOSPITAL DISCHARGE DATA; PREGNANCY-RELATED MORTALITY; SPONTANEOUS PRETERM BIRTH; UTERINE CONTRACTILITY; RACIAL DISPARITIES; VAGINAL BIRTH; UNITED-STATES; COMPLICATIONS; BLACK; OUTCOMES AB BACKGROUND: There are profound racial and ethnic disparities in obstetric outcomes in the United States, but little is known about disparities in risk of postpartum hemorrhage (PPH). We explored the association of race and ethnicity on the risk of PPH due to uterine atony with sequential adjustment for possible mediating factors. METHODS: This analysis was based on the Nationwide Inpatient Sample, from between 2005 and 2008. The frequencies of atonic PPH and atonic PPH resulting in transfusion or hysterectomy were estimated. We developed multivariable logistic regression models to estimate the odds of these outcomes in maternal racial/ethnic groups by sequentially adding potential mediators. RESULTS: Hispanic ethnicity and Asian/Pacific Islander race were associated with a statistically significant increased odds of atonic PPH in comparison with Caucasians, despite adjustment for potential mediators (adjusted odds ratio [OR] for Hispanics: 1.21, 99% confidence interval [1.18, 1.25]; for Asians/Pacific Islanders: 1.31 [1.25, 1.38], with Caucasians as reference). Similar results were observed for these racial/ethnic groups for atonic PPH resulting in transfusion or hysterectomy. CONCLUSION: Hispanic ethnicity and Asian/Pacific Islander race are significant risk factors for atonic PPH independent of measured potential mediators; biological differences may play a role. (Anesth Analg 2012;115:1127-36) C1 [Leffert, Lisa R.; Bateman, Brian T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bryant, Allison] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. [Mhyre, Jill M.] Univ Michigan Hlth Syst, Dept Anesthesiol, Ann Arbor, MI USA. [Hoban, Rebecca A.] Tufts Med Ctr, Dept Newborn Med, Boston, MA USA. [Hoban, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Global Hlth, Boston, MA 02114 USA. [Yakoob, Mohammad Y.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02114 USA. RP Bateman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM BBateman@partners.org FU Robert Wood Johnson Foundation [RWJF-67875]; T32 Training Grant [GM007592] FX This publication was supported by the Amos Medical Faculty Development : Award of the Robert Wood Johnson Foundation, Grant no. RWJF-67875 to A.B.) and T32 Training Grant GM007592 (to B.T.B.). NR 46 TC 15 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2012 VL 115 IS 5 BP 1127 EP 1136 DI 10.1213/ANE.0b013e3182691e62 PG 10 WC Anesthesiology SC Anesthesiology GA 032ZO UT WOS:000310762100019 PM 22886840 ER PT J AU Gilman, SE Breslau, J Trinh, NH Fava, M Murphy, JM Smoller, JW AF Gilman, Stephen E. Breslau, Joshua Trinh, Nhi-Ha Fava, Maurizio Murphy, Jane M. Smoller, Jordan W. TI Epidemiologic Evidence Concerning the Bereavement Exclusion in Major Depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Gilman, Stephen E.; Murphy, Jane M.; Smoller, Jordan W.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gilman, Stephen E.; Trinh, Nhi-Ha; Fava, Maurizio; Murphy, Jane M.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Breslau, Joshua] RAND Corp, Santa Monica, CA USA. RP Gilman, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 677 Huntington Ave, Boston, MA 02115 USA. EM sgilman@hsph.harvard.edu RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 NR 4 TC 2 Z9 2 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2012 VL 69 IS 11 BP 1179 EP 1180 PG 2 WC Psychiatry SC Psychiatry GA 032CI UT WOS:000310689200011 PM 23117639 ER PT J AU Cote, CJ AF Cote, Charles J. TI American Academy of Pediatrics Sedation Guidelines Are We There Yet? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material ID HIGH-DOSE DEXMEDETOMIDINE; PROCEDURAL SEDATION; ADVERSE EVENTS; PULSE OXIMETRY; CHLORAL HYDRATE; DEVELOPMENTAL-DISABILITIES; EMERGENCY-DEPARTMENT; PROPOFOL SEDATION; OPERATING-ROOM; SINGLE-BLIND C1 [Cote, Charles J.] Harvard Univ, Sch Med, Dept Anesthesia & Crit Care, Div Pediat Anesthesia, Boston, MA USA. [Cote, Charles J.] Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. RP Cote, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Pediat Anesthesia, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org NR 47 TC 1 Z9 1 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD NOV PY 2012 VL 166 IS 11 BP 1067 EP 1069 PG 3 WC Pediatrics SC Pediatrics GA 032BI UT WOS:000310686400013 PM 22965766 ER PT J AU Hiremath, SV Ding, D Farringdon, J Cooper, RA AF Hiremath, Shivayogi V. Ding, Dan Farringdon, Jonathan Cooper, Rory A. TI Predicting Energy Expenditure of Manual Wheelchair Users With Spinal Cord Injury Using a Multisensor-Based Activity Monitor SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Arm ergometry test; Energy expenditure; Physical activity; Rehabilitation; Spinal cord injuries; Wheelchairs ID FREE-LIVING ADULTS; PHYSICAL-ACTIVITY; PARAPLEGIA; AGREEMENT AB Objective: To develop and evaluate new energy expenditure (EE) prediction models for manual wheelchair users (MWUs) with spinal cord injury (SCI) based on a commercially available multisensor-based activity monitor. Design: Cross-sectional. Setting: Laboratory. Participants: Volunteer sample of MWUs with SCI (N=45). Intervention: Subjects were asked to perform 4 activities including resting, wheelchair propulsion, arm-ergometer exercise, and deskwork. Criterion EE using a metabolic cart and raw sensor data from a multisensor-based activity monitor was collected during each of these activities. Main Outcome Measures: Two new EE prediction models including a general model and an activity-specific model were developed using enhanced all-possible regressions on 36 MWUs and tested on the remaining 9 MWUs. Results: The activity-specific and general EE prediction models estimated the EE significantly better than the manufacturer's model. The average EE estimation error using the manufacturer's model and the new general and activity-specific models for all activities combined was -55.31% (overestimation), 2.30% (underestimation), and 4.85%, respectively. The average EE estimation error using the manufacturer's model, the new general model, and activity-specific models for various activities varied from -19.10% to -89.85%, -18.13% to 25.13%, and -4.31% to 9.93%, respectively. Conclusions: The predictors for the new models were based on accelerometer and demographic variables, indicating that movement and subject parameters were necessary in estimating the EE. The results indicate that the multisensor activity monitor with new prediction models can be used to estimate EE in MWUs with SCI during wheelchair-related activities mentioned in this study. C1 [Hiremath, Shivayogi V.; Ding, Dan; Cooper, Rory A.] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs VA, Pittsburgh, PA 15206 USA. [Hiremath, Shivayogi V.; Ding, Dan; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Ding, Dan; Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Farringdon, Jonathan] BodyMedia Inc, Pittsburgh, PA USA. RP Ding, D (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs VA, 6425 Penn Ave, Pittsburgh, PA 15206 USA. EM dad5@pitt.edu OI Farringdon, Jonathan/0000-0001-5977-3700 FU Rehabilitation Engineering Research Center on Interactive Exercise Technologies and Exercise Physiology for Persons with Disabilities [H133E070029]; National Institute on Disability and Rehabilitation Research; VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering [B3142C] FX Supported by the Rehabilitation Engineering Research Center on Interactive Exercise Technologies and Exercise Physiology for Persons with Disabilities (grant no. H133E070029), funded by the National Institute on Disability and Rehabilitation Research; and by the VA Center of Excellence for Wheelchairs and Associated Rehabilitation Engineering (grant no. B3142C). The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 18 TC 12 Z9 12 U1 0 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2012 VL 93 IS 11 BP 1937 EP 1943 DI 10.1016/j.apmr.2012.05.004 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 031VQ UT WOS:000310671100008 PM 22609119 ER PT J AU Kocher, MS Frank, JS Nasreddine, AY Safran, MR Philippon, MJ Sekiya, JK Kelly, BT Byrd, JWT Guanche, CA Martin, HD Clohisy, JC Mohtadi, NG Griffin, DR Sampson, TG Leunig, M Larson, CM Ilizaliturri, VM McCarthy, JC Gambacorta, PG AF Kocher, Mininder S. Frank, Jeremy S. Nasreddine, Adam Y. Safran, Marc R. Philippon, Marc J. Sekiya, Jon K. Kelly, Bryan T. Byrd, J. W. Thomas Guanche, Carlos A. Martin, Hal D. Clohisy, John C. Mohtadi, Nick G. Griffin, Damian R. Sampson, Thomas G. Leunig, Michael Larson, Christopher M. Ilizaliturri, Victor M., Jr. McCarthy, Joseph C. Gambacorta, Peter G. TI Intra-Abdominal Fluid Extravasation During Hip Arthroscopy: A Survey of the MAHORN Group SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID ABDOMINAL COMPARTMENT SYNDROME; COMPLICATIONS; BRADYCARDIA; JOINT AB Purpose: The purpose of this study was to survey experts in the field of hip arthroscopy from the Multicenter Arthroscopy of the Hip Outcomes Research Network (MAHORN) group to determine the frequency of symptomatic intra-abdominal fluid extravasation (IAFE) after arthroscopic hip procedures, identify potential risk factors, and develop preventative measures and treatment strategies in the event of symptomatic IAFE. Methods: A survey was sent to all members of the MAHORN group. Surveys collected data on general hip arthroscopy settings, including pump pressure and frequency of different hip arthroscopies performed, as well as details on cases of symptomatic IAFE. Responses to the survey were documented and analyzed. Results: Fifteen hip arthroscopists from the MAHORN group were surveyed. A total of 25,648 hip arthroscopies between 1984 and 2010 were reviewed. Arthroscopic procedures included capsulotomies, labral reattachment after acetabuloplasty, peripheral compartment arthroscopy, and osteoplasty of the femoral head-neck junction. Of the arthroscopists, 7 (47%) had 1 or more cases of IAFE (40 cases reported). The prevalence of IAFE in this study was 0.16% (40 of 25,650). Significant risk factors associated with IAFE were higher arthroscopic fluid pump pressure (P = .004) and concomitant iliopsoas tenotomy (P < .001). In all 40 cases, the condition was successfully treated without long-term sequelae. Treatment options included observation, intravenous furosemide, and Foley catheter placement, as well as 1 case of laparotomy. Conclusions: Symptomatic IAFE after hip arthroscopy is a rare occurrence, with an approximate prevalence of 0.16%. Prevention of IAFE should include close intra-operative and postoperative monitoring of abdominal distention, core body temperature, and hemodynamic stability. Concomitant iliopsoas tenotomy and high pump pressures may be risk factors leading to symptomatic IAFE. Level of Evidence: Level IV, therapeutic case series. C1 [Kocher, Mininder S.; Frank, Jeremy S.; Nasreddine, Adam Y.; Gambacorta, Peter G.] Childrens Hosp Boston, Div Sports Med, Boston, MA USA. [Safran, Marc R.] Stanford Univ, Div Sports Med, Redwood City, CA USA. [Philippon, Marc J.] Steadman Philippon Res Inst, Vail, CO USA. [Sekiya, Jon K.] Univ Michigan, Div Sports Med, Ann Arbor, MI 48109 USA. [Kelly, Bryan T.] Hosp Special Surg, New York, NY 10021 USA. [Byrd, J. W. Thomas] Nashville Sports Med Ctr, Nashville, TN USA. [Guanche, Carlos A.] So Calif Orthopaed Inst, Van Nuys, CA USA. [Martin, Hal D.] Hip Clin, Oklahoma City, OK USA. [Clohisy, John C.] Washington Univ Orthopaed, St Louis, MO USA. [Sampson, Thomas G.] Post St Orthopaed & Sports Med, San Francisco, CA USA. [Larson, Christopher M.] Minnesota Orthoped Sports Med Inst, Minneapolis, MN USA. [McCarthy, Joseph C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mohtadi, Nick G.] Univ Calgary, Div Orthopaed Surg, Calgary, AB, Canada. [Griffin, Damian R.] Univ Warwick, Orthopaed Surg Res Grp, Coventry CV4 7AL, W Midlands, England. [Leunig, Michael] Schulthess Clin, Hip Serv, Zurich, Switzerland. [Ilizaliturri, Victor M., Jr.] Natl Rehabil Inst Mexico, Mexico City, DF, Mexico. RP Kocher, MS (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Sports Med, 300 Longwood Ave, Boston, MA 02115 USA. EM mininder.kocher@childrens.harvard.edu RI Leunig, Michael/E-7951-2017; OI Leunig, Michael/0000-0002-2036-5416; Guanche, Carlos/0000-0002-4897-5443 NR 14 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD NOV PY 2012 VL 28 IS 11 BP 1654 EP + DI 10.1016/j.arthro.2012.04.151 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 029NW UT WOS:000310503500015 PM 22989716 ER PT J AU Poghosyan, H Sheldon, LK Cooley, ME AF Poghosyan, Hermine Sheldon, Lisa Kennedy Cooley, Mary E. TI The Impact of Computed Tomography Screening for Lung Cancer on Smoking Behaviors A Teachable Moment? SO CANCER NURSING LA English DT Article DE Current smokers; Helical computed tomography; Lung cancer; Screening; Smoking abstinence ID CIGARETTE-SMOKING; ACTION PROJECT; UNITED-STATES; FOLLOW-UP; CESSATION; CT; PROGRAM; EPIDEMIOLOGY; UPDATE; TRIAL AB Background: Helical computed tomography (CT) has emerged as a potential screening test for lung cancer. An important component of care surrounding the use of this technology is the impact of screening on decisions surrounding smoking cessation. Objective: The aim of this article was to conduct an integrative review of literature on the impact of lung cancer screening with CT on smoking behaviors of current smokers. Methods: Ganong's [Res Nurs Health. 1987; 10(1): 1-11] guidelines were used to conduct this integrative review. Computerized databases were used to identify relevant articles. Data were extracted from the studies, and then content analysis was used to synthesize the findings. Results: Nine studies were identified and reviewed. The quit rate among participants ranged from 6.6% to 42% after screening. Among current smokers, smoking abstinence was associated with older age, worse pulmonary function, and having multiple abnormal CT findings. Motivation to quit smoking, within the next 30 days, ranged from 14% to 35% among smokers. Factors associated with increased motivation were older age, lower nicotine addiction, fewer lung cancer symptoms, higher self-efficacy, and acknowledgment of the advantages of quitting smoking. Conclusions: Participants undergoing lung cancer screening had increased motivation to quit smoking. Computed tomographic screening for lung cancer appears to be a teachable moment to address smoking cessation. Implications for Practice: Screening for lung cancer is only one step to fight lung cancer. Incorporating smoking cessation interventions along with the use of technology is necessary to fight this deadly disease. C1 [Poghosyan, Hermine; Sheldon, Lisa Kennedy] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis F Cantor Ctr Res Nursing & Patient Care S, Boston, MA 02115 USA. RP Poghosyan, H (reprint author), Univ Massachusetts, Coll Nursing & Hlth Sci, 100 Morrissey Blvd, Boston, MA 02125 USA. EM hermine.poghosyan002@umb.edu OI Sheldon, Lisa Kennedy/0000-0002-5958-8529 NR 40 TC 6 Z9 6 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD NOV-DEC PY 2012 VL 35 IS 6 BP 466 EP 475 DI 10.1097/NCC.0b013e3182406297 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA 030KF UT WOS:000310568900015 ER PT J AU Underhill, ML Lally, RM Kiviniemi, MT Murekeyisoni, C Dickerson, SS AF Underhill, Meghan L. Lally, Robin M. Kiviniemi, Marc T. Murekeyisoni, Christine Dickerson, Suzanne S. TI Living My Family's Story Identifying the Lived Experience in Healthy Women at Risk for Hereditary Breast Cancer SO CANCER NURSING LA English DT Article DE Genetics; Hereditary breast cancer risk; Nursing; Phenomenology ID QUALITY-OF-LIFE; BILATERAL PROPHYLACTIC MASTECTOMY; SURGICAL ADJUVANT BREAST; OVARIAN-CANCER; PSYCHOLOGICAL IMPACT; YOUNGER WOMEN; SCREENING-PROGRAM; BRCA MUTATION; PREVENTION; HISTORY AB Background: Based on known or suggested genetic risk factors, a growing number of women now live with knowledge of a potential cancer diagnosis that may never occur. Given this, it is important to understand the meaning of living with high risk for hereditary breast cancer. Objective: The objective of the study was to explore how women at high risk for hereditary breast cancer (1) form self-identity, (2) apply self-care strategies toward risk, and (3) describe the meaning of care through a high-risk breast program. Methods: Interpretive hermeneutic phenomenology guided the qualitative research method. Women at high risk for hereditary breast cancer were recruited from a high-risk breast program. Open-ended interview questions focused on experiences living as women managing high risk for breast cancer. Consistent with hermeneutic methodology, the principal investigator led a team to analyze the interview transcripts. Results: Twenty women participated in in-depth interviews. Analysis revealed that women describe their own identity based on their family story and grieve over actual and potential familial loss. This experience influences self-care strategies, including seeking care from hereditary breast cancer risk experts for early detection and prevention, as well as maintaining a connection for early treatment "when" diagnosis occurs. Conclusions: Healthy women living with high risk for hereditary breast cancer are living within the context of their family cancer story, which influences how they define themselves and engage in self-care. Implications for Practice: Findings present important practical, research, and policy information regarding health promotion, psychosocial assessment, and support for women living with hereditary breast cancer risk. C1 [Underhill, Meghan L.] Univ Massachusetts, Dana Farber Canc Inst, Boston, MA 02115 USA. [Underhill, Meghan L.] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. [Lally, Robin M.; Kiviniemi, Marc T.; Dickerson, Suzanne S.] SUNY Buffalo, Buffalo, NY 14260 USA. [Murekeyisoni, Christine; Dickerson, Suzanne S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Underhill, ML (reprint author), Univ Massachusetts, Dana Farber Canc Inst, 450 Brookline Ave,LW517, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu RI Kiviniemi, Marc/B-8513-2013 OI Kiviniemi, Marc/0000-0002-1299-8416 FU Sigma Theta Tau Gamma Kappa Chapter Research Award FX Funding was received from the Sigma Theta Tau Gamma Kappa Chapter Research Award (Dr Underhill). NR 51 TC 4 Z9 4 U1 2 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD NOV-DEC PY 2012 VL 35 IS 6 BP 493 EP 504 DI 10.1097/NCC.0b013e31824530fa PG 12 WC Oncology; Nursing SC Oncology; Nursing GA 030KF UT WOS:000310568900018 PM 22544165 ER PT J AU Wang, JH AF Wang, Jia-huai TI Pull and push: Talin activation for integrin signaling SO CELL RESEARCH LA English DT Editorial Material ID STRUCTURAL BASIS; DOMAIN; TAIL AB The inside-out signaling of integrins regulates the ligand-binding affinity of the cell surface receptors in response to changes in the environment for cell survival. The specific binding to the cytoplasmic tail of integrin's beta subunit by the intracellular protein talin is the key step of inside-out signaling. A "pull-push" mechanism has been proposed to explain how the PIP2-enriched membrane disrupts the dual auto-inhibition of the N-terminal talin-FERM domain by the C-terminal talin-rod domain such that activated talin-FERM can reach the beta-tail for integrin activation. C1 [Wang, Jia-huai] Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. [Wang, Jia-huai] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Wang, JH (reprint author), Peking Univ, Coll Life Sci, Beijing 100871, Peoples R China. EM jwang@red.dfci.harvard.edu NR 13 TC 12 Z9 12 U1 0 U2 9 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD NOV PY 2012 VL 22 IS 11 BP 1512 EP 1514 DI 10.1038/cr.2012.103 PG 3 WC Cell Biology SC Cell Biology GA 033IY UT WOS:000310789500001 PM 22777425 ER PT J AU Xu, HS Yi, BA Chien, KR AF Xu, Huansheng Yi, B. Alexander Chien, Kenneth R. TI In vivo reprogramming for heart disease SO CELL RESEARCH LA English DT Editorial Material ID CARDIAC FIBROBLASTS; CARDIOMYOCYTES; THERAPY; CELLS AB The term "lineage reprogramming" is typically used to describe the conversion of one differentiated somatic cell type into another without transit through a pluripotent intermediate. Two recent reports in Nature demonstrate that such a conversion can be achieved in the heart in situ, and suggest a novel, regenerative approach for the development of cardiac therapeutics. C1 [Xu, Huansheng; Yi, B. Alexander; Chien, Kenneth R.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Xu, Huansheng; Yi, B. Alexander; Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Chien, KR (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. EM kchien@harvard.edu FU NHLBI NIH HHS [U01 HL100408] NR 15 TC 3 Z9 3 U1 1 U2 6 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD NOV PY 2012 VL 22 IS 11 BP 1521 EP 1523 DI 10.1038/cr.2012.101 PG 3 WC Cell Biology SC Cell Biology GA 033IY UT WOS:000310789500004 PM 22751090 ER PT J AU Johnson, RA Uddin, T Aktar, A Mohasin, M Alam, MM Chowdhury, F Harris, JB LaRocque, RC Bufano, MK Yu, YA Wu-Freeman, Y Leung, DT Sarracino, D Krastins, B Charles, RC Xu, P Kovac, P Calderwood, SB Qadri, F Ryan, ET AF Johnson, Russell A. Uddin, Taher Aktar, Amena Mohasin, M. Alam, Mohammad Murshid Chowdhury, Fahima Harris, Jason B. LaRocque, Regina C. Bufano, Meagan Kelly Yu, Yanan Wu-Freeman, Ying Leung, Daniel T. Sarracino, David Krastins, Bryan Charles, Richelle C. Xu, Peng Kovac, Pavol Calderwood, Stephen B. Qadri, Firdausi Ryan, Edward T. TI Comparison of Immune Responses to the O-Specific Polysaccharide and Lipopolysaccharide of Vibrio cholerae O1 in Bangladeshi Adult Patients with Cholera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID B-CELL RESPONSES; INFECTION-DERIVED IMMUNITY; CONJUGATE VACCINES; STRUCTURAL-ANALYSIS; HOUSEHOLD CONTACTS; SEROTYPE INABA; CORE REGION; ANTIBODY; TOXIN; PROTECTION AB Immunity against Vibrio cholerae O1 is serogroup specific, and serogrouping is defined by the O-specific polysaccharide (OSP) part of lipopolysaccharide (LPS). Despite this, human immune responses to V. cholerae OSP have not previously been characterized. We assessed immune responses against V. cholerae OSP in adults with cholera caused by V. cholerae O1 El Tor serotype Inaba or Ogawa in Dhaka, Bangladesh, using O1 OSP-core-bovine serum albumin (OSPc:BSA) conjugates; responses targeted OSP in these conjugates. Responses of Inaba-infected patients to Inaba OSP and LPS increased significantly in IgG, IgM, and IgA isotypes from the acute to convalescent phases of illness, and the responses correlated well between OSP and LPS (R = 0.86, 0.73, and 0.91, respectively; P < 0.01). Plasma IgG, IgM, and IgA responses to Ogawa OSP and LPS in Ogawa-infected patients also correlated well with each other (R = 0.60, 0.60, and 0.92, respectively; P < 0.01). Plasma IgM responses to Inaba OSP and Ogawa OSP correlated with the respective serogroup-specific vibriocidal antibodies (R = 0.80 and 0.66, respectively; P < 0.001). Addition of either OSPc: BSA or LPS, but not BSA, to vibriocidal assays inhibited vibriocidal responses in a comparable and concentration-dependent manner. Mucosal IgA immune responses to OSP and LPS were also similar. Our study is the first to characterize anti-OSP immune responses in patients with cholera and suggests that responses targeting V. cholerae LPS, including vibriocidal responses that correlate with protection against cholera, predominantly target OSP. Induction of anti-OSP responses may be associated with protection against cholera, and our results may support the development of a vaccine targeting V. cholerae OSP. C1 [Harris, Jason B.; LaRocque, Regina C.; Bufano, Meagan Kelly; Yu, Yanan; Wu-Freeman, Ying; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Johnson, Russell A.; Uddin, Taher; Aktar, Amena; Mohasin, M.; Alam, Mohammad Murshid; Chowdhury, Fahima; Leung, Daniel T.; Qadri, Firdausi] ICDDR B, Ctr Vaccine Sci, Dhaka, Bangladesh. [LaRocque, Regina C.; Yu, Yanan; Leung, Daniel T.; Charles, Richelle C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Harris, Jason B.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Sarracino, David; Krastins, Bryan] Thermo Fisher Sci, Cambridge, MA USA. [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD USA. [Calderwood, Stephen B.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM etryan@partners.org RI Xu, Peng/K-7036-2012; Kovac, Pavol/B-8813-2008; OI Kovac, Pavol/0000-0001-5044-3449; leung, daniel/0000-0001-8401-0801 FU ICDDR,B; Intramural Research Program of the National Institutes of Health, NIDDK; National Institutes of Health, National Institute of Allergy and Infectious Diseases [U01 AI058935, R03 AI063079, U01 AI077883, K08 AI100923, K08 AI089721]; Fogarty International Center, Training Grant in Vaccine Development and Public Health [TW005572]; American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases [TW05572]; Career Development Awards [K01 TW07409, TW07144]; Fogarty International Clinical Research Scholars Award [R24 TW007988]; Swedish International Development Cooperation Agency; Howard Hughes Medical Institute; American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund; Harvard Institute for Global Health Postdoctoral Fellowship in Global Infectious Diseases FX This research was supported by the ICDDR,B and by the Intramural Research Program of the National Institutes of Health, NIDDK, and extramural grants from the National Institutes of Health, including the National Institute of Allergy and Infectious Diseases (U01 AI058935 [S. B. C. and E. T. R.], R03 AI063079 [F. Q.], U01 AI077883 [E. T. R.], K08 AI100923 and K08 AI089721 [R. C. C.]), the Fogarty International Center, Training Grant in Vaccine Development and Public Health (TW005572 [T. U., M. M. A., and F. Q.]), an American Recovery and Reinvestment Act (ARRA) Postdoctoral Fellowship in Global Infectious Diseases (TW05572 [D. T. L.]), Career Development Awards (K01 TW07409 [J.B.H.] and TW07144 [R. C. L.]), and a Fogarty International Clinical Research Scholars Award (R24 TW007988 [R.A.J. and T. U.]), as well as by the Swedish International Development Cooperation Agency (F. Q.), a Physician Scientist Early Career Award from the Howard Hughes Medical Institute (R. C. L.), a Postdoctoral Fellowship in Tropical Infectious Diseases from the American Society for Tropical Medicine & Hygiene-Burroughs Wellcome Fund (D. T. L.), and the Harvard Institute for Global Health Postdoctoral Fellowship in Global Infectious Diseases (D.T.L). NR 53 TC 19 Z9 19 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2012 VL 19 IS 11 BP 1712 EP 1721 DI 10.1128/CVI.00321-12 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 030IF UT WOS:000310563700002 PM 22993410 ER PT J AU Kanwal, F Hoang, T Chrusciel, T Kramer, JR El-Serag, HB Dominitz, JA Asch, SM AF Kanwal, Fasiha Hoang, Tuyen Chrusciel, Timothy Kramer, Jennifer R. El-Serag, Hashem B. Dominitz, Jason A. Asch, Steven M. TI Process of Care for Hepatitis C Infection Is Linked to Treatment Outcome and Virologic Response SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Quality of Care; Performance; Chronic Liver Disease; Indicator ID QUALITY-OF-CARE; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; VIRUS-INFECTION; COMBINATION THERAPY; RANDOMIZED-TRIAL; UNITED-STATES; PREDICTORS; MANAGEMENT; DIAGNOSIS AB BACKGROUND & AIMS: Process of care-based measures are used commonly to assess the quality of medical care provided to patients with chronic hepatitis C virus (HCV) infection. However, the links between these processes and patient outcomes are not clear. METHODS: We conducted a large retrospective cohort study of 34,749 patients with HCV infection identified from the national Veterans Administration HCV Clinical Case Registry between 2003 and 2006. We examined the relationship between meeting process-based measures of HCV care (categorized into pretreatment, preventive or comorbid care, and treatment monitoring domains) and antiviral treatment-related outcomes. For each domain, we defined optimum care as receipt of all indicated care processes in that domain. Study end points were rates of antiviral treatment, treatment completion, and sustained virologic response (SVR), adjusted for patient demographics, comorbidities, use of health services, and intrafacility clustering. RESULTS: Patients who received optimum pretreatment care were significantly more likely to receive antiviral treatment (odds ratio [OR], 3.2; 95% confidence interval [CI], 2.9-3.5), complete treatment (OR, 1.26; 95% CI, 1.13-1.43), and achieve an SVR (OR, 1.29; 95% CI, 1.01-1.65), than those with suboptimum pretreatment care. Optimum preventive or comorbidity care also independently was associated with receipt of antiviral treatment (OR, 1.36; 95% CI, 1.23-1.51), but not with completion of treatment or SVR. Optimum treatment monitoring was associated with a nonsignificant trend toward achieving an SVR (OR, 1.22; 95% CI, 0.95-1.56). CONCLUSIONS: Optimum care for HCV infection-particularly the care delivered before treatment-is associated with increased rates of treatment and SVR. These data could be used to guide clinical policy as newer, more-effective treatments become available. C1 [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Houston Vet Adm Hlth Serv Res & Dev Ctr Excellenc, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. [Kanwal, Fasiha; Hoang, Tuyen; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Chrusciel, Timothy] Greater Los Angeles VA Healthcare Syst, Dept Med, Los Angeles, CA USA. [Chrusciel, Timothy] John Cochran VA Med Ctr, St Louis, MO USA. [Dominitz, Jason A.] VA Puget Hlth Care Syst, Seattle, WA USA. [Asch, Steven M.] VA Palo Alto, VA Hlth Serv Res & Dev Ctr Excellence, Hlth Serv Res & Dev Serv, Palo Alto, CA USA. [Asch, Steven M.] Stanford Univ, Coll Med, Dept Med, Palo Alto, CA 94304 USA. RP Kanwal, F (reprint author), Michael E DeBakey VA Med Ctr, Houston Vet Adm Hlth Serv Res & Dev Ctr Excellenc, Hlth Serv Res & Dev Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM fasiha.kanwal@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs [IIR-07-111] FX This material is based on work supported by the Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs, grant IIR-07-111 (F.K.). NR 34 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2012 VL 10 IS 11 BP 1270 EP + DI 10.1016/j.cgh.2012.07.015 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 033FS UT WOS:000310780200020 PM 22841970 ER PT J AU Gu, F Molano, I Ruiz, P Sun, LY Gilkeson, GS AF Gu, Fei Molano, Ivan Ruiz, Philip Sun, Lingyun Gilkeson, Gary S. TI Differential effect of allogeneic versus syngeneic mesenchymal stem cell transplantation in MRL/lpr and (NZB/NZW)F1 mice SO CLINICAL IMMUNOLOGY LA English DT Article DE Mesenchymal stem cells; Systemic lupus erythematosus; Allogeneic; Syngeneic ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; MARROW STROMAL CELLS; T-REGULATORY CELLS; RENAL-DISEASE; MURINE MODEL; PROLIFERATION; SUPPRESSION; EXPRESSION; THERAPY; INHIBIT AB MSC are being explored as a promising novel treatment for SLE. In this study, we: 1) assessed the differential effects of allogeneic versus syngeneic MSC transplantation on lupus-like disease, 2) explored the mechanisms by which MSC modulate disease, and 3) investigated whether lupus-derived-MSC have intrinsic immunomodulatory defects. We showed that in MRL/lpr mice and (NZB/NZW)F1 mice, both B6-MSC and lupus-MSC from young mice ameliorated SLE-like disease and reduced splenic CD3+CD4+ T lymphocytes and CD19+CD21+ B lymphocytes. However, lupus-MSC from older (NZB/NZW)F1 mice did not reduce spleen weights, glomerular IgG deposits, renal pathology, interstitial inflammation, CD3+CD4+ T lymphocytes or CD19+CD21+ B lymphocytes significantly. Thus MSC transplantation ameliorates SLE-like disease partly through decreasing CD4+ T cell and naive mature B cell numbers. Allogeneic MSC may be preferred over syngeneic lupus-derived-MSC given the decreased overall effectiveness of post-lupus-derived-MSC, which appears partially due to disease and not exclusively intrinsic defects in the MSC themselves. Published by Elsevier Inc. C1 [Gu, Fei; Sun, Lingyun] Nanjing Univ, Dept Rheumatol & Immunol, Affiliated Drum Tower Hosp, Sch Med, Nanjing 210008, Jiangsu, Peoples R China. [Gu, Fei; Molano, Ivan; Gilkeson, Gary S.] Med Univ S Carolina, Div Rheumatol & Immunol, Dept Med, Charleston, SC 29425 USA. [Gilkeson, Gary S.] Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29403 USA. [Ruiz, Philip] Univ Miami, Sch Med, Dept Pathol, Miami, FL 33136 USA. RP Sun, LY (reprint author), Nanjing Univ, Dept Rheumatol & Immunol, Affiliated Drum Tower Hosp, Sch Med, 321 Zhong Shan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM lingyunsun2001@yahoo.com.cn; gilkeson@musc.edu FU Lupus Foundation of America; Major International (Regional) Joint Research Project of China [81120108021]; National Natural Science Foundation of China [30972736] FX This work was supported by a grant from the Lupus Foundation of America, the Major International (Regional) Joint Research Project of China (No. 81120108021), and National Natural Science Foundation of China (No. 30972736). NR 30 TC 27 Z9 30 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2012 VL 145 IS 2 BP 142 EP 152 DI 10.1016/j.clim.2012.08.012 PG 11 WC Immunology SC Immunology GA 031WB UT WOS:000310672200011 PM 23041504 ER PT J AU Ritchie, C Richman, J Sobko, H Bodner, E Phillips, B Houston, T AF Ritchie, Christine Richman, Joshua Sobko, Heather Bodner, Eric Phillips, Barrett Houston, Thomas TI The E-Coach transition support computer telephony implementation study: Protocol of a randomized trial SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Care transitions; Interactive voice response; Telehealth ID INTERACTIVE VOICE RESPONSE; CARE; INTERVENTION AB Background: Patients requiring complex care are at high risk during the transition from one setting of care to another. Effective interventions to support care transitions have been designed but are very resource intensive. Telemonitoring has been considered as an approach to enhance care transition support, but many telemonitoring systems require special equipment or web-based interfaces to interact with patients and caregivers. Methods/design: In this paper we report our protocol for developing and testing E-Coach, an interactive voice response (IVR)-enhanced care transition intervention that monitors patients at home using their personal phone. The elements described include 1) development of an IVR monitoring system that will be based on Coleman's four pillars of care transition support; 2) development of a web-based "dashboard" of IVR responses that alert care transition nurses (CTN) of patient/caregiver concerns after discharge and allow documentation by the CTN when patients/caregivers are called; 3) pilot testing of the IVR system by patients and providers with refinement of the system based on patient/provider input; and 4) a pragmatic protocol for formal testing through a randomized controlled trial (RCT) of the E-Coach intervention in congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) patients admitted to a large tertiary hospital. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ritchie, Christine; Bodner, Eric] Univ Alabama Birmingham UAB, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Richman, Joshua] Birmingham VA Med Ctr, Birmingham, AL 35222 USA. [Sobko, Heather] Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35294 USA. [Phillips, Barrett; Houston, Thomas] Univ Massachusetts, Sch Med, Div Hlth Informat & Implementat Sci, Worcester, MA 01655 USA. RP Ritchie, C (reprint author), Univ Calif San Francisco, Dept Med, Div Geriatr, 3333 Calif St,Suite 380, San Francisco, CA 94118 USA. EM critchie@uab.edu; jrichman@mail.dopm.uab.edu; hsobko@uab.edu; ebodner@uab.edu; BarrettD.Phillips@umassmed.edu; thomas.houston@umassmed.edu RI Houston, Thomas/F-2469-2013 FU Agency for Healthcare Research and Quality Care of Complex Patients grant [R18-HS017786-02] FX This project is supported by an Agency for Healthcare Research and Quality Care of Complex Patients grant # R18-HS017786-02. NR 13 TC 5 Z9 5 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2012 VL 33 IS 6 BP 1172 EP 1179 DI 10.1016/j.cct.2012.08.007 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 033UA UT WOS:000310825400008 PM 22922245 ER PT J AU Al-Jiboury, H Kaunitz, JD AF Al-Jiboury, Hala Kaunitz, Jonathan D. TI Gastroduodenal mucosal defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Review DE estrogen; gastrointestinal defense; matrix metalloproteinase-2; oxidative stress; trefoil factors ID DUODENAL BICARBONATE SECRETION; GASTRIC OXIDATIVE STRESS; GLUCAGON-LIKE PEPTIDE-2; HELICOBACTER-PYLORI; EPITHELIAL-CELLS; HEME OXYGENASE-1; INJURY; ACTIVATION; MECHANISM; EXPRESSION AB Purpose of review To review recent developments in the field of gastroduodenal mucosal defense. Recent findings Research in the field of gastroduodenal mucosal defense is shifting from animal models of mucosal injury towards the elucidation of molecular mechanisms that protect the mucosa at the cellular level. Accordingly, the recent literature is focused on endogenous antioxidants such as mitochondrial superoxide dismutase (SOD), and heme oxygenase-1, mucosal receptors such as the Toll-like receptors and protease-activated receptors, endogenous proteins with protective effects such as the matrix metalloproteinases, heat-inducible factors and trefoil factors, protective functions of submucosal mononuclear cells, junctional proteins affecting mucosal permeability, and hormone-mediated protective mechanisms mediated by estrogens, vasoactive peptides, and other hormones. Summary These new published findings contribute to our overall understanding of gastroduodenal defense and suggest innovative avenues of future research and possible novel therapeutic targets. C1 [Al-Jiboury, Hala] Cedars Sinai Med Residency Program, Los Angeles, CA USA. [Kaunitz, Jonathan D.] Greater Los Angeles Vet Affairs Healthcare Syst, WLAVA Med Ctr, Los Angeles, CA USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Dept Med, Los Angeles, CA USA. [Kaunitz, Jonathan D.] UCLA Sch Med, Dept Surg, Los Angeles, CA USA. [Kaunitz, Jonathan D.] CURE Digest Dis Res Ctr, Dept Med, Los Angeles, CA USA. [Kaunitz, Jonathan D.] Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles VAMC, MD Bldg 114,Room 217E, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU Department of Veterans Affairs Merit Review Award; NIH-NIDDK [R01 54221] FX The authors declare no competing interests with the content of this article. Supported by a Department of Veterans Affairs Merit Review Award (J.D.K.), and NIH-NIDDK R01 54221 (J.D.K.). NR 34 TC 4 Z9 4 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2012 VL 28 IS 6 BP 594 EP 601 DI 10.1097/MOG.0b013e328358d56c PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NA UT WOS:000310358200009 PM 22954689 ER PT J AU Matthews, LT Smit, JA Cu-Uvin, S Cohan, D AF Matthews, Lynn T. Smit, Jennifer A. Cu-Uvin, Susan Cohan, Deborah TI Antiretrovirals and safer conception for HIV-serodiscordant couples SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE antiretrovirals as prevention; conception; fertility; HIV prevention; HIV-serodiscordance; perinatal HIV transmission; sexual HIV transmission ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERSISTENT MITOCHONDRIAL DYSFUNCTION; RANDOMIZED CONTROLLED-TRIAL; SERO-DISCORDANT COUPLES; SEMINAL PLASMA SAMPLES; PREEXPOSURE PROPHYLAXIS; VIRAL LOAD; SOUTH-AFRICA; INFECTED WOMEN; FERTILITY INTENTIONS AB Purpose of review Many men and women living with HIV and their uninfected partners attempt to conceive children. HIV-prevention science can be applied to reduce sexual transmission risk while respecting couples' reproductive goals. Here we discuss antiretrovirals as prevention in the context of safer conception for HIV-serodiscordant couples. Recent findings Antiretroviral therapy (ART) for the infected partner and pre-exposure prophylaxis (PrEP) for the uninfected partner reduce the risk of heterosexual HIV transmission. Several demonstration projects suggest the feasibility and acceptability of antiretroviral (ARV)s as periconception HIV-prevention for HIV-serodiscordant couples. The application of ARVs to periconception risk reduction may be limited by adherence. Summary For male-infected (M+F-) couples who cannot access sperm processing and female-infected (F+M-) couples unwilling to carry out insemination without intercourse, ART for the infected partner, PrEP for the uninfected partner, combined with treatment for sexually transmitted infections, sex limited to peak fertility, and medical male circumcision (for F+M couples) provide excellent, well tolerated options for reducing the risk of periconception HIV sexual transmission. C1 [Matthews, Lynn T.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Matthews, Lynn T.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02114 USA. [Smit, Jennifer A.] Univ Witwatersrand, Maternal Adolescent & Child Hlth Div MatCH, Durban, South Africa. [Cu-Uvin, Susan] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Cohan, Deborah] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Serv, San Francisco, CA 94143 USA. RP Matthews, LT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM ltmatthe@bidmc.harvard.edu FU K23 award [MH095655]; William and Flora Hewlett Foundation FX L.T.M. is supported by a K23 award (MH095655). J.A.S. is supported by the William and Flora Hewlett Foundation. We thank Dr. David R. Bangsberg and Dr. Matthew J. Ehrlich for important contributions to the article. NR 119 TC 41 Z9 42 U1 4 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2012 VL 7 IS 6 BP 569 EP 578 DI 10.1097/COH.0b013e328358bac9 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028IN UT WOS:000310416100012 PM 23032734 ER PT J AU Yuki, K Bu, WM Xi, J Sen, M Shimaoka, M Eckenhoff, RG AF Yuki, Koichi Bu, Weiming Xi, Jin Sen, Mehmet Shimaoka, Motomu Eckenhoff, Roderic G. TI Isoflurane binds and stabilizes a closed conformation of the leukocyte function-associated antigen-1 SO FASEB JOURNAL LA English DT Article DE immunomodulation; photolabeling; rigid docking; volatile anesthetics ID I-LIKE DOMAIN; INTERCELLULAR-ADHESION MOLECULES; STRUCTURAL BASIS; INTEGRIN ALPHA(L)BETA(2); MONOCLONAL-ANTIBODY; AFFINITY STATES; LIGAND-BINDING; LUNG INJURY; LFA-1; ACTIVATION AB We previously demonstrated that isoflurane targets lymphocyte function-associated antigen-1 (LFA-1), a critical adhesion molecule for leukocyte arrest. However, it remains to be determined how isoflurane interacts with the full ectodomain LFA-1 and modulates its conformation and function. Isoflurane binding sites on the full ectodomain LFA-1 were probed by photolabeling using photoactivatable isoflurane (azi-isoflurane). The adducted residues were determined by liquid chromatography/mass spectrometry analysis. Separately, docking simulations were performed to predict binding sites. Point mutations were introduced around isoflurane binding sites. The significance of isoflurane's effect was assessed in both intracellular adhesion molecule-1 (ICAM-1) binding assays and epitope mapping of activation-sensitive antibodies using flow cytometry. Two isoflurane binding sites were identified using photolabeling and were further validated by the docking simulation: one at the hydrophobic pocket in the ICAM-1 binding domain (the alpha I domain); the other at the beta I domain. Mutagenesis of the alpha'1 helix showed that isoflurane binding sites at the beta I domain were significantly important in modulating LFA-1 function and conformation. Epitope mapping using activation-sensitive antibodies suggested that isoflurane stabilized LFA-1 in the closed conformation. This study suggested that isoflurane binds to both the alpha I and beta I domains allosteric to the ICAM-1 binding site, and that isoflurane binding stabilizes LFA-1 in the closed conformation.-Yuki, K., Bu, W., Xi, J., Sen, M., Shimaoka, M., Eckenhof, R. G. Isoflurane binds and stabilizes a closed conformation of the leukocyte function-associated antigen-1. FASEB J. 26, 4408-4417 (2012). www.fasebj.org C1 [Yuki, Koichi] Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Yuki, Koichi; Sen, Mehmet; Shimaoka, Motomu] Immune Dis Inst, Boston, MA USA. [Bu, Weiming; Xi, Jin; Eckenhoff, Roderic G.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. RP Yuki, K (reprint author), Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, 300 Longwood Ave, Boston, MA 02115 USA. EM koichi.yuki@childrens.harvard.edu FU U.S. National Institutes of Health [P01GM55876, K08GM101345] FX The authors thank W. P. Dailey (University of Pennsylvania) for providing azi-isoflurane, and T. A. Springer (Immune Disease Institute) for providing reagents and insightful comments. This work was supported by grants from the U.S. National Institutes of Health, P01GM55876 (R.G.E.) and K08GM101345 (K.Y.). The authors declare no conflicts of interest. NR 50 TC 9 Z9 10 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2012 VL 26 IS 11 BP 4408 EP 4417 DI 10.1096/fj.12-212746 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 030MG UT WOS:000310574200005 PM 22815384 ER PT J AU Khalili, H Higuchi, LM Ananthakrishnan, AN Manson, JE Feskanich, D Richter, JM Fuchs, CS Chan, AT AF Khalili, Hamed Higuchi, Leslie M. Ananthakrishnan, Ashwin N. Manson, Joann E. Feskanich, Diane Richter, James M. Fuchs, Charles S. Chan, Andrew T. TI Hormone Therapy Increases Risk of Ulcerative Colitis but not Crohn's Disease SO GASTROENTEROLOGY LA English DT Article DE Inflammatory Bowel Disease; IBD; Predisposition; Menopause ID INFLAMMATORY-BOWEL-DISEASE; OLMSTED COUNTY; PROSPECTIVE COHORT; BARRIER FUNCTION; NURSES HEALTH; US WOMEN; PREVALENCE; METAANALYSIS; MINNESOTA; VALIDITY AB BACKGROUND & AIMS: Estrogen has been proposed to modulate gut inflammation through an effect on estrogen receptors found on gastrointestinal epithelial and immune cells. The role of postmenopausal hormone therapy on risk of Crohn's disease (CD) and ulcerative colitis (UC) is unclear. METHODS: We conducted a prospective cohort study of 108,844 postmenopausal US women (median age, 54 years) enrolled in 1976 in the Nurses' Health Study without a prior history of CD or UC. Every 2 years, we have updated information on menopause status, postmenopausal hormone use, and other risk factors. Self-reported diagnoses of CD and UC were confirmed through medical record review by 2 gastroenterologists who were blinded to exposure information. We used Cox proportional hazards models to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Through 2008, with more than 1.8 million person-years of follow-up, we documented 138 incident cases of CD and 138 cases of UC. Compared with women who never used hormones, the multivariate-adjusted HR for UC was 1.71 (95% CI, 1.07-2.74) among women who currently used hormones and 1.65 (95% CI, 1.03-2.66) among past users. The risk of UC appeared to increase with longer duration of hormone use (P-trend = .04) and decreased with time since discontinuation. There was no difference in risk according to the type of hormone therapy used (estrogen vs estrogen plus progestin). In contrast, we did not observe an association between current use of hormones and risk of CD (multivariate-adjusted HR, 1.19; 95% CI, 0.78-1.82). The effect of hormones on risk of UC and CD was not modified by age, body mass index, or smoking. CONCLUSIONS: In a large prospective cohort of women, postmenopausal hormone therapy was associated with an increased risk of UC but not CD. These findings indicate that pathways related to estrogens might mediate the pathogenesis of UC. C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, Boston, MA 02114 USA. [Khalili, Hamed; Higuchi, Leslie M.; Ananthakrishnan, Ashwin N.; Richter, James M.; Fuchs, Charles S.; Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Higuchi, Leslie M.] Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. [Manson, Joann E.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Feskanich, Diane; Fuchs, Charles S.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Chan, AT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Div Gastroenterol, 55 Fruit St,GRJ 728A, Boston, MA 02114 USA. EM achan@partners.org FU Crohn's and Colitis Foundation of America; National Institute of Diabetes and Digestive and Kidney Diseases [K08 DK064256]; American Gastroenterological Association; [R01 CA137178]; [P01 CA87969]; [P30 DK043351] FX Supported by grants R01 CA137178, P01 CA87969, P30 DK043351, and K08 DK064256. A. T. C. is a Damon Runyon Cancer Research Foundation Clinical Investigator, H. K. is supported by a career development award from the Crohn's and Colitis Foundation of America, L. M. H. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K08 DK064256), and A.N.A. is supported by a career development award from the American Gastroenterological Association. NR 36 TC 26 Z9 28 U1 0 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2012 VL 143 IS 5 BP 1199 EP 1206 DI 10.1053/j.gastro.2012.07.096 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 028XU UT WOS:000310459700032 PM 22841783 ER PT J AU Rutherford, A King, LY Hynan, LS Vedvyas, C Lin, WY Lee, WM Chung, RT AF Rutherford, Anna King, Lindsay Y. Hynan, Linda S. Vedvyas, Chetan Lin, Wenyu Lee, William M. Chung, Raymond T. CA ALF Study Grp TI Development of an Accurate Index for Predicting Outcomes of Patients With Acute Liver Failure SO GASTROENTEROLOGY LA English DT Article DE Prognostic Factor; Cell Death Marker; Liver Disease Progression; Risk Factor ID FULMINANT HEPATIC-FAILURE; MEDIATED APOPTOSIS; CASPASE ACTIVATION; EARLY INDICATORS; PROGNOSIS; ACETAMINOPHEN; TRANSPLANTATION; NECROSIS; CRITERIA; INJURY AB BACKGROUND & AIMS: Patients with acute liver failure (ALF) have high mortality and frequently require liver transplantation (LT); few reliable prognostic markers are available. Levels of M30, a cleavage product of cytokeratin-18 caspase, are significantly increased in serum samples from patients with ALF who die or undergo LT. We developed a prognostic index for ALF based on level of M30 and commonly measured clinical variables (called the Acute Liver Failure Study Group [ALFSG] index) and compared its accuracy with that of the King's College criteria (KCC) and Model for End Stage Liver Disease (MELD). We also validated our model in an independent group of patients with ALF. METHODS: Serum levels of M30 and M65 antigen (the total cytokeratin-18 fragment, a marker of apoptosis and necrosis) were measured on 3 of the first 4 days following admission of 250 patients with ALF. Logistic regression was used to determine whether the following factors, measured on day 1, were associated with LT or death: age, etiology; coma grade; international normalized ratio (INR); serum pH; body mass index; levels of creatinine, bilirubin, phosphorus, arterial ammonia, and lactate; and log(10) M30 and log10 M65. The area under the receiver operating characteristic (AUROC) was calculated for the ALFSG and other indices. RESULTS: Coma grade, INR, levels of bilirubin and phosphorus, and log10 M30 value at study entry most accurately identified patients who would require LT or die. The ALFSG index identified these patients with 85.6% sensitivity and 64.7% specificity. Based on comparison of AUROC values, the ALFSG Index (AUROC, 0.822) better identified patients most likely to require LT or die than the KCC (AUROC, 0.654) or MELD (AUROC, 0.704) (P = .0002 and P = .0010, respectively). We validated these findings in a separate group of 250 patients with ALF. CONCLUSIONS: The ALFSG index, a combination of clinical markers and measurements of the apoptosis biomarker M30, better predicts outcomes of patients with ALF than the KCC or MELD; ClinicalTrials.gov, number NCT00518440. C1 [King, Lindsay Y.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Rutherford, Anna; King, Lindsay Y.] Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. [Rutherford, Anna] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA. [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, Div Biostat, Dallas, TX 75390 USA. [Hynan, Linda S.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [Vedvyas, Chetan] Harvard Univ, Sch Med, Boston, MA USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Warren 10, Boston, MA 02114 USA. EM RTChung@partners.org OI Hynan, Linda/0000-0002-4642-7769 FU NIH [K24 DK078772, K24DK078772]; [U01DK58369]; [R21DK077716] FX Supported by U01DK58369, R21DK077716, and NIH K24 DK078772 (funding for Dr Raymond T. Chung from NIH K24DK078772). NR 26 TC 37 Z9 38 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2012 VL 143 IS 5 BP 1237 EP 1243 DI 10.1053/j.gastro.2012.07.113 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 028XU UT WOS:000310459700036 PM 22885329 ER PT J AU Levin, MC Lidberg, U Jirholt, P Adiels, M Wramstedt, A Gustafsson, K Greaves, DR Li, S Fazio, S Linton, MF Olofsson, SO Boren, J Gjertsson, I AF Levin, M. C. Lidberg, U. Jirholt, P. Adiels, M. Wramstedt, A. Gustafsson, K. Greaves, D. R. Li, S. Fazio, S. Linton, M. F. Olofsson, S-O Boren, J. Gjertsson, I. TI Evaluation of macrophage-specific promoters using lentiviral delivery in mice SO GENE THERAPY LA English DT Article DE macrophage; promoter; lentivirus ID GENE-THERAPY; INNATE IMMUNITY; DEFICIENT MICE; EXPRESSION; ATHEROSCLEROSIS; CELLS; VECTOR; CD68; TRANSDUCTION; MACROSIALIN AB In gene therapy, tissue-specific promoters are useful tools to direct transgene expression and improve efficiency and safety. Macrophage-specific promoters (MSPs) have previously been published using different delivery systems. In this study, we evaluated five different MSPs fused with green fluorescent protein (GFP) to delineate the one with highest specificity using lentiviral delivery. We compared three variants of the CD68 promoter (full length, the 343-bp proximal part and the 150-bp proximal part) and two variants (in forward and reverse orientation) of a previously characterized synthetic promoter derived from elements of transcription factor genes. We transduced a number of cell lines and primary cells in vitro. In addition, hematopoietic stem cells were transduced with MSPs and transferred into lethally irradiated recipient mice. Fluorescence activated cell sorting analysis was performed to determine the GFP expression in different cell populations both in vitro and in vivo. We showed that MSPs can efficiently be used for lentiviral gene delivery and that the 150-bp proximal part of the CD68 promoter provides primarily macrophage-specific expression of GFP. We propose that this is the best currently available MSP to use for directing transgene expression to macrophage populations in vivo using lentiviral vectors. C1 [Jirholt, P.; Gjertsson, I.] Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. [Gustafsson, K.] UCL, Inst Child Hlth, Mol Immunol Unit, London, England. [Greaves, D. R.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. [Li, S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Li, S.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Fazio, S.; Linton, M. F.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, Nashville, TN USA. [Levin, M. C.; Lidberg, U.; Adiels, M.; Wramstedt, A.; Olofsson, S-O; Boren, J.; Gjertsson, I.] Univ Gothenburg, Wallenberg Lab, Dept Mol & Clin Med, Gothenburg, Sweden. RP Levin, MC (reprint author), Sahlgrens Univ Hosp, Wallenberg Lab, Gothenburg 41345, Sweden. EM malin.levin@wlab.gu.se OI Greaves, David/0000-0003-2856-9410 FU Swedish Research Council; VINNOVA Foundation; IngaBritt and Arne Lundgren Foundation; Swedish Foundation for Strategic Research; Sahlgrenska University Hospital ALF research grants; NIH [HL105375, HL57986, HL106845, HL65709] FX We thank Louise Henningsson, Kristina Skalen, Elin Stenfeldt and Maria Heyden (Gothenburg University) for expert technical assistance; Yan Ru Su and John Blakemore (Vanderbilt University) for stimulating discussions and technical expertise; and Rosie Perkins (Gothenburg University) for editing the manuscript. This work was supported by the Swedish Research Council; the VINNOVA Foundation; the IngaBritt and Arne Lundgren Foundation; the Swedish Foundation for Strategic Research; the Sahlgrenska University Hospital ALF research grants; and NIH Grants HL105375, HL57986, HL106845 and HL65709. NR 29 TC 9 Z9 9 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 2012 VL 19 IS 11 BP 1041 EP 1047 DI 10.1038/gt.2011.195 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 034AA UT WOS:000310841300001 PM 22130447 ER PT J AU Walker, RJ Smalls, BL Hernandez-Tejada, MA Campbell, JA Davis, KS Egede, LE AF Walker, Rebekah J. Smalls, Brittany L. Hernandez-Tejada, Melba A. Campbell, Jennifer A. Davis, Kimberly S. Egede, Leonard E. TI Effect of diabetes fatalism on medication adherence and self-care behaviors in adults with diabetes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Fatalism; Medication adherence; Self-care; Diabetes ID AFRICAN-AMERICANS; DEPRESSION; QUESTIONNAIRE; METAANALYSIS; VALIDITY; SCALE AB Objective: Diabetes fatalism is defined as "a complex psychological cycle characterized by perceptions of despair, hopelessness, and powerlessness" and associated with poor glycemic control. This study examined the association between diabetes fatalism and medication adherence and self-care behaviors in adults with diabetes. Methods: Data on 378 subjects with type 2 diabetes recruited from two primary care clinics in the Southeastern United States were examined. Previously validated scales were used to measure diabetes fatalism, medication adherence, diabetes knowledge and diabetes selfcare behaviors (diet, physical activity, blood sugar testing and foot care). Multiple linear regression was used to assess the independent effect of diabetes fatalism on medication adherence and self-care behaviors controlling for relevant covariates. Results: Fatalism correlated significantly with medication adherence (r=0.24, P<.001), diet (r=-0.26, P<.001), exercise (r=-0.20, P<.001) and blood sugar testing (r=-0.19, P<.001). In the linear regression model, diabetes fatalism was significantly associated with medication adherence [beta=0.029, 95% confidence interval (CI) 0.016, 0.043], diabetes knowledge (beta=-0.042, 95% CI -0.001, -0.084), diet (beta=-0.063, 95% CI -0.039, -0.087), exercise (beta=-0.055, 95% CI -0.028, -0.083) and blood sugar testing (beta=-0.055, 95% CI -0.023, -0.087). There was no significant association between diabetes fatalism and foot care (beta=-0.018, 95% CI -0.047, 0.011). The association between diabetes fatalism and medication adherence, diabetes knowledge and diabetes self-care behaviors did not change significantly when depression was added to the models, suggesting that the associations are independent of depression. Conclusion: Diabetes fatalism is associated with poor medication adherence and self-care and may be an important target for education and skills interventions in diabetes care. In addition, the effect of diabetes fatalism is independent of depression, suggesting that interventions that target depression may not be sufficient to deal with diabetes fatalism. (C) 2012 Elsevier Inc. All rights reserved. C1 [Walker, Rebekah J.; Smalls, Brittany L.; Hernandez-Tejada, Melba A.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Davis, Kimberly S.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA REAP, Ctr Dis Prevent & Hlth Intervent Diverse Populat, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute for Diabetes, Digestive and Kidney Disease [T35DK007431] FX Supported by Grant #T35DK007431 from the National Institute for Diabetes, Digestive and Kidney Disease. NR 25 TC 18 Z9 19 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2012 VL 34 IS 6 BP 598 EP 603 DI 10.1016/j.genhosppsych.2012.07.005 PG 6 WC Psychiatry SC Psychiatry GA 031WA UT WOS:000310672100003 PM 22898447 ER PT J AU Maldonado, JR Nguyen, LH Schader, EM Brooks, JO AF Maldonado, Jose R. Nguyen, Long H. Schader, E. Merritt Brooks, John O., III TI Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Alcohol; Benzodiazepines; Withdrawal; Lorazepam; Diazepam; Symptom triggered; Loading method ID INTENSIVE-CARE-UNIT; PRACTICE GUIDELINE; MANAGEMENT; DEPENDENCE; LORAZEPAM; CHLORDIAZEPOXIDE; DETOXIFICATION; METAANALYSIS; MEDICATIONS; PREVALENCE AB Objectives: The objectives were to compare the efficacy of a benzodiazepine loading versus a symptom-triggered protocol in the management of alcohol withdrawal. Methods: We conducted a prospective, randomized, controlled trial including 47 consecutive patients admitted to one of two tertiary care medical centers who developed alcohol withdrawal syndrome. Patients were randomly assigned to either a benzodiazepine loading protocol or a symptom-triggered treatment protocol. The Clinical Institute Withdrawal Assessment for Alcohol-Revised scale (CIWA-Ar) was recorded throughout the length of stay, along with measures of autonomic system functioning. Results: The average rate of change of CIWA-Ar scores was -1.5 +/- 1.3 for the symptom-triggered group and -2.3 +/- 2.5 for the loading group. Average rate of change for systolic blood pressure was -2.7 +/- 5.3 for the symptom-triggered group and -2.3 +/- 6.4 for the loading group. There was no significant difference between the rates of change for either group on either measure. Similarly, there was no significant difference in total benzodiazepine use between groups. Within 72 h of treatment, 69.6% of patients in the loading group were free of withdrawal symptoms versus 41.7% in the symptom-triggered group, a difference not reaching statistical significance. Conclusions: This study did not reveal clear evidence of a clinical advantage for choosing either treatment method. (C) 2012 Elsevier Inc. All rights reserved. C1 [Maldonado, Jose R.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Nguyen, Long H.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schader, E. Merritt] Community Solut, Morgan Hill, CA USA. [Brooks, John O., III] Univ Calif Los Angeles, Semel Inst, Los Angeles, CA USA. RP Maldonado, JR (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. EM jrm@stanford.edu NR 51 TC 9 Z9 9 U1 4 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2012 VL 34 IS 6 BP 611 EP 617 DI 10.1016/j.genhosppsych.2012.06.016 PG 7 WC Psychiatry SC Psychiatry GA 031WA UT WOS:000310672100005 PM 22898443 ER PT J AU Lu, MW Carlson, KF Duckart, JP Dobscha, SK AF Lu, Mary W. Carlson, Kathleen F. Duckart, Jonathan P. Dobscha, Steven K. TI The effects of age on initiation of mental health treatment after positive PTSD screens among Veterans Affairs primary care patients SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Veterans/psychology; Posttraumatic stress disorders; Mass screening ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN; IRAQ; VALIDATION; DEPRESSION; SERVICES AB Objective: The objective was to examine differences by age in mental health treatment initiation in Veterans Health Administration (VA) primary care patients after positive posttraumatic stress disorder (PTSD) screens. Methods: This was a retrospective cohort study of 71,039 veterans who were administered PTSD screens during primary care encounters in 2007 at four Pacific Northwest VA medical center sites and who had no specialty mental health clinic visits or PTSD diagnoses recorded in the year before screening. Main outcome measures were attendance of any specialty mental health clinic visits or receipt of any antidepressant medication in the year after a positive PTSD screen. Results: Older veterans, compared with veterans less than 30 years old, were less likely to attend any specialty mental health visits after positive PTSD screens [adjusted odds ratios (ORs) ranged from .57 to .12, all P<.001], and veterans 75 years and older were less likely to receive any antidepressant medication (adjusted OR=.56, P<.001). Conclusions: Initiation of mental health treatment among veterans who screen positive for PTSD varies significantly by age. Further research should examine whether this is due to differences in base rates of PTSD, treatment preferences, provider responses to screens or other age-related barriers to mental health treatment. Published by Elsevier Inc. C1 [Lu, Mary W.] Portland VA Med Ctr, Mental Hlth & Neurosci Div, Portland, OR 97239 USA. [Lu, Mary W.; Dobscha, Steven K.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Carlson, Kathleen F.; Duckart, Jonathan P.; Dobscha, Steven K.] Portland VA Med Ctr, Portland Ctr Study Chron Comorbid Mental & Phys D, Portland, OR 97239 USA. [Carlson, Kathleen F.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Lu, MW (reprint author), Portland VA Med Ctr, Mental Hlth & Neurosci Div, POB 1034,P3MHR, Portland, OR 97239 USA. EM Mary.Lu@va.gov FU VA Health Services Research and Development Service (HSRD) [REA 06-174, CDA 08-025]; Pacific Northwest Mental Illness Research and Education and Clinical Center FX This work was supported by VA Health Services Research and Development Service (HSR&D) grants REA 06-174 and CDA 08-025, and the Pacific Northwest Mental Illness Research and Education and Clinical Center. The authors acknowledge Bentson McFarland, M.D., Ph.D.; Jean O'Malley, M.P.H.; Maya O'Neil, M.S., Ph.D.; Alex Linke, B.S.; Molly DeLorit, B.A.; Sondra K. Long, B.A.; and Linda Ganzini, M.D., for their assistance. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. NR 30 TC 10 Z9 10 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2012 VL 34 IS 6 BP 654 EP 659 DI 10.1016/j.genhosppsych.2012.07.002 PG 6 WC Psychiatry SC Psychiatry GA 031WA UT WOS:000310672100012 PM 22898446 ER PT J AU Wu, RI Mark, EJ Hunt, JL AF Wu, Roseann I. Mark, Eugene J. Hunt, Jennifer L. TI Staining for acid-fast bacilli in surgical pathology: practice patterns and variations SO HUMAN PATHOLOGY LA English DT Article DE Acid-fast bacilli; Tuberculosis; Quality control ID TUBERCULOSIS; SPUTUM; LUNG AB Analysis of acid-fast bacilli stains on sputum smears for the diagnosis of tuberculosis has a long history, but quality control for acid-fast bacilli in histologic sections is not as well established. In tissues, necrotizing granulomas are closely linked to positive cultures for mycobacteria. However, the practices of pathologists examining acid-fast bacilli in surgical specimens are not well described in the literature. This study characterizes practice patterns related to the histologic interpretation of acid-fast bacilli stains. A survey invitation was sent to 1299 pathologists including members of the Pulmonary Pathology Society and randomly selected fellows of the College of American Pathologists. Twenty-one questions inquired about demographics, ordering and interpreting acid-fast bacilli stains, reporting, and correlation. Of the 392 responses (30.2% response rate), 363 respondents review acid-fast bacilli stains on histologic sections. Approximately half of respondents practice in an academic setting, with the other half in community practice. Most respondents examine the entire acid-fast bacilli slide with the x40 objective; approximately half confirm the organisms under oil immersion at x100. There was considerable variation in when an acid-fast bacilli stain is ordered, as well as possible additional workup for negative cases, reporting of results, correlation with clinical and culture findings, and training. Many respondents reported never having been taught a general approach to acid-fast bacilli interpretation. There is substantial variation in practice patterns involving all aspects of ordering, histologic examination, and reporting of acid-fast bacilli stains. Future efforts to standardize the interpretation of acid-fast bacilli stains can potentially improve the diagnosis of mycobacterial disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Wu, Roseann I.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wu, RI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM riwu@partners.org NR 11 TC 1 Z9 3 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2012 VL 43 IS 11 BP 1845 EP 1851 DI 10.1016/j.humpath.2012.01.006 PG 7 WC Pathology SC Pathology GA 031PN UT WOS:000310654500007 PM 22542129 ER PT J AU Chetty, R Gill, P Govender, D Bateman, A Chang, HJ Deshpande, V Driman, D Gomez, M Greywoode, G Jaynes, E Lee, CS Locketz, M Rowsell, C Rullier, A Serra, S Shepherd, N Szentgyorgyi, E Vajpeyi, R Wang, LM Bateman, A AF Chetty, Runjan Gill, Pelvender Govender, Dhirendra Bateman, Adrian Chang, Hee Jin Deshpande, Vikram Driman, David Gomez, Marisa Greywoode, Godman Jaynes, Eleanor Lee, C. Soon Locketz, Michael Rowsell, Corwyn Rullier, Anne Serra, Stefano Shepherd, Neil Szentgyorgyi, Eva Vajpeyi, Rajkumar Wang, Lai Mun Bateman, Andrew TI International study group on rectal cancer regression grading: interobserver variability with commonly used regression grading systems SO HUMAN PATHOLOGY LA English DT Article DE Rectal cancer; Neoadjuvant chemoradiation; Regression grading ID PREOPERATIVE CHEMORADIOTHERAPY; NEOADJUVANT THERAPY; CHEMORADIATION; RADIATION; SURGERY; STAGE AB The aim of this study was to ascertain the level of concordance among gastrointestinal pathologists for regression grading in rectal cancers treated with neoadjuvant chemoradiation. Seventeen gastrointestinal pathologists participated using the Mandard, Dworak, and modified rectal cancer regression grading systems to grade 10 representative slides that were selected from 10 cases of rectal cancer treated with long-course neoadjuvant chemoradiation. The slides were scanned with a whole-slide scanner generating dynamic digitized images. The results showed very little concordance across the 3 grading systems, with values of 0.28, 0.35, and 0.38 for the Mandard, Dworak, and modified rectal cancer regression grading systems, respectively. In only 1 of 10 study cases was there unanimous grading concordance using the modified rectal cancer regression grading system. It was felt that these systems lacked precision and clarity for reproducible, accurate regression grading. The study concluded that there was a need for a simple, reproducible regression grading system with clear criteria, a cumulative or composite score taking into account all sections of the tumor bed that is sampled rather than the worst section (highest grade), and there should be a uniform method of sampling of these specimens. (C) 2012 Elsevier Inc. All rights reserved. C1 [Chetty, Runjan] John Radcliffe Hosp, Dept Cellular Pathol, Biomed Res Ctr, Nuffield Dept Clin Lab Sci,Acad Ctr, Oxford OX3 9DU, England. [Chetty, Runjan; Gill, Pelvender; Greywoode, Godman; Wang, Lai Mun] Univ Oxford, Oxford OX3 9DU, England. [Govender, Dhirendra; Locketz, Michael] Univ Cape Town, Div Anat Pathol, NHLS Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Bateman, Adrian; Jaynes, Eleanor] Univ Hosp Southampton NHS Fdn Trust, Dept Cellular Pathol, Southampton SO16 6YD, Hants, England. [Chang, Hee Jin] Natl Canc Ctr, Res Inst & Hosp, Ctr Colorectal Canc, Goyang 410769, South Korea. [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Driman, David] Univ Western Ontario, London Hlth Sci Ctr, Dept Pathol, London, ON N6A 5A5, Canada. [Gomez, Marisa] Hosp Navarra, Dept Pathol, Pamplona 31002, Spain. [Lee, C. Soon] Royal Prince Alfred Hosp, Sydney, NSW 2751, Australia. [Lee, C. Soon] Univ Western Sydney, Sch Med, Discipline Pathol, Dept Anat Pathol, Liverpool, NSW, Australia. [Rowsell, Corwyn] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Pathol, Toronto, ON M4N 3M5, Canada. [Rullier, Anne] CHU Bordeaux, Dept Pathol, F-33076 Bordeaux, France. [Serra, Stefano; Szentgyorgyi, Eva; Vajpeyi, Rajkumar] Univ Toronto, Dept Pathol, Univ Hlth Network, Toronto, ON M5G 2C4, Canada. [Shepherd, Neil] Cheltenham Gen Hosp, Gloucestershire Cellular Pathol Lab, Cheltenham GL53 7AN, Glos, England. [Bateman, Andrew] Southampton Univ Hosp NHS Trust, Dept Oncol, Southampton SO16 6YD, Hants, England. RP Chetty, R (reprint author), John Radcliffe Hosp, Dept Cellular Pathol, Biomed Res Ctr, Nuffield Dept Clin Lab Sci,Acad Ctr, Level 1,Headley Way, Oxford OX3 9DU, England. EM runjan.chetty@ndcls.ox.ac.uk OI Bateman, Adrian/0000-0003-2222-4104; serra, stefano/0000-0002-3258-2637; Locketz, Michael/0000-0002-3917-3895 NR 21 TC 32 Z9 34 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2012 VL 43 IS 11 BP 1917 EP 1923 DI 10.1016/j.humpath.2012.01.020 PG 7 WC Pathology SC Pathology GA 031PN UT WOS:000310654500016 PM 22575264 ER PT J AU Ravikoff, JE Cole, EB Korzenik, JR AF Ravikoff, Jessica E. Cole, Elisabeth B. Korzenik, Joshua R. TI Barriers to enrollment in inflammatory bowel disease randomized controlled trials: An investigation of patient perspectives SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE inflammatory bowel disease; trial design; barriers to enrollment ID PREVENTION TRIALS; CLINICAL-TRIALS; WILLINGNESS; PARTICIPATE AB Background: Despite a sizeable inflammatory bowel disease (IBD) population in the United States, large trials in IBD have difficulty recruiting patients. Reasons for low enrollment are uncertain. Our objective was to investigate specific barriers to enrollment in clinical trials by determining aspects of study design, disease state, demographics, and previous experiences with research that influence a patient's willingness to participate. Methods: Patients with Crohn's disease (CD) and ulcerative colitis (UC) at the Massachusetts General Hospital Crohn's and Colitis Center were surveyed. Results: Most participants (61%) had participated in some clinical research previously, although 50% of those were not interested in participating in a future study. Frequent doctor visits (69%), requirement of colonoscopy (55%), or sigmoidoscopy (49%), and blinding (46%) were the biggest deterrent study requirements. With each addition of one of these components, potential enrollment fell from 43.2% (86) to 14.6% (29) interested patients. Respondents were likely to participate in studies that were open label (60%), initially randomized then open label (57.6%), or saw the same doctor (52.5%). Among those disinclined to participate, strategies to boost enrollment included monetary compensation, an open-label component, or providing the same doctor at each visit. Men and patients who were currently flaring were more likely to participate. Conclusions: Elements of study design negatively and positively influence willingness to participate. Invasive procedures, randomization, and frequent visits negatively influenced willingness to participate and as each of these components are added, a significant additive percent of potential subjects are lost. Strategies to further identify barriers to enrollment within IBD study populations should be pursued. (Inflamm Bowel Dis 2012;) C1 [Ravikoff, Jessica E.; Cole, Elisabeth B.; Korzenik, Joshua R.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ravikoff, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM jravikoff@partners.org NR 7 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2012 VL 18 IS 11 BP 2092 EP 2098 DI 10.1002/ibd.22872 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 026DD UT WOS:000310252500013 PM 22241674 ER PT J AU Liu, SS Buvanendran, A Rathmell, JP Sawhney, M Bae, JJ Moric, M Perros, S Pope, AJ Poultsides, L Della Valle, CJ Shin, NS McCartney, CJL Ma, Y Shah, M Wood, MJ Manion, SC Sculco, TP AF Liu, Spencer S. Buvanendran, Asokumar Rathmell, James P. Sawhney, Mona Bae, James J. Moric, Mario Perros, Stephen Pope, Ashley J. Poultsides, Lazaros Della Valle, Craig J. Shin, Naomi S. McCartney, Colin J. L. Ma, Yan Shah, Mahendrakumar Wood, Monica J. Manion, Smith C. Sculco, Thomas P. TI Predictors for moderate to severe acute postoperative pain after total hip and knee replacement SO INTERNATIONAL ORTHOPAEDICS LA English DT Article ID UNITED-STATES; ARTHROPLASTY; CONSUMPTION; ANALGESIA AB The ability to identify and focus care to patients at higher risk of moderate to severe postoperative pain should improve analgesia and patient satisfaction, and may affect reimbursement. We undertook this multi-centre cross-sectional study to identify preoperative risk factors for moderate to severe pain after total hip (THR) and knee (TKR) replacement. A total of 897 patients were identified from electronic medical records. Preoperative information and anaesthetic technique was gained by retrospective chart review. The primary outcomes were moderate to severe pain (pain score a parts per thousand yenaEuro parts per thousand 4/10) at rest and with activity on postoperative day one. Logistic regression was performed to identify predictors for moderate to severe pain. Moderate to severe pain was reported by 20 % at rest and 33 % with activity. Predictors for pain at rest were female gender (OR 1.10 with 95 % CI 1.01-1.20), younger age (0.96, 0.94-0.99), increased BMI (1.02, 1.01-1.03), TKR vs. THR (3.21, 2.73-3.78), increased severity of preoperative pain at the surgical site (1.15, 1.03-1.30), preoperative use of opioids (1.63, 1.32-2.01), and general anaesthesia (8.51, 2.13-33.98). Predictors for pain with activity were TKR vs. THR (1.42, 1.28-1.57), increased severity of preoperative pain at the surgical site (1.11, 1.04-1.19), general anaesthesia (9.02, 3.68-22.07), preoperative use of anti-convulsants (1.78, 1.32-2.40) and anti-depressants (1.50, 1.08-2.80), and prior surgery at the surgical site (1.28, 1.05-1.57). Our findings provide clinical guidance for preoperative stratification of patients for more intensive management potentially including education, nursing staffing, and referral to specialised pain management. C1 [Liu, Spencer S.; Bae, James J.] Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA. [Ma, Yan] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA. [Poultsides, Lazaros; Sculco, Thomas P.] Hosp Special Surg, Dept Orthoped Surg, New York, NY 10021 USA. [Buvanendran, Asokumar; Moric, Mario; Shah, Mahendrakumar] Rush Univ, Dept Anesthesiol, Med Ctr, Chicago, IL 60612 USA. [Buvanendran, Asokumar; Moric, Mario; Della Valle, Craig J.; Shah, Mahendrakumar] Rush Med Coll, Chicago, IL 60612 USA. [Della Valle, Craig J.] Rush Univ, Dept Orthoped Surg, Med Ctr, Chicago, IL 60612 USA. [Rathmell, James P.; Perros, Stephen; Shin, Naomi S.; Wood, Monica J.; Manion, Smith C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Rathmell, James P.; Perros, Stephen; Shin, Naomi S.; Wood, Monica J.; Manion, Smith C.] Harvard Univ, Sch Med, Boston, MA USA. [Sawhney, Mona; Pope, Ashley J.; McCartney, Colin J. L.] Univ Toronto, Toronto, ON, Canada. [Sawhney, Mona; Pope, Ashley J.; McCartney, Colin J. L.] Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON M4N 3M5, Canada. RP Liu, SS (reprint author), Hosp Special Surg, Dept Anesthesiol, 535 E 70th St, New York, NY 10021 USA. EM anessl@yahoo.com OI Moric, Mario/0000-0003-2844-8168 FU Clinical Translational Science Center [NIH UL1-RR024996]; Smith Nephew; Zimmer; Exactech FX Funding was provided by the Department of Anesthesiology, Hospital for Special Surgery. Dr. Ma was partially supported by Clinical Translational Science Center (NIH UL1-RR024996). Dr. Della Valle is a consultant for Biomet, Convatec and Smith & Nephew and receives research support from Smith & Nephew and Zimmer. Dr. Sculco receives research support from Exactech. NR 23 TC 39 Z9 39 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 J9 INT ORTHOP JI Int. Orthop. PD NOV PY 2012 VL 36 IS 11 BP 2261 EP 2267 DI 10.1007/s00264-012-1623-5 PG 7 WC Orthopedics SC Orthopedics GA 026CW UT WOS:000310251600012 PM 22842653 ER PT J AU Rudders, SA Geyer, BC Banerji, A Phipatanakul, W Clark, S Camargo, CA AF Rudders, Susan A. Geyer, Brian C. Banerji, Aleena Phipatanakul, Wanda Clark, Sunday Camargo, Carlos A., Jr. TI Obesity is not a risk factor for repeat epinephrine use in the treatment of anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID EMERGENCY-DEPARTMENT; FOOD C1 [Rudders, Susan A.] Rhode Isl Hosp, Div Asthma & Allergy, Dept Pediat, Providence, RI 02903 USA. [Geyer, Brian C.] Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. [Geyer, Brian C.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Banerji, Aleena; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Phipatanakul, Wanda] Childrens Hosp Boston, Div Allergy & Immunol, Dept Pediat, Boston, MA USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. RP Rudders, SA (reprint author), Rhode Isl Hosp, Div Asthma & Allergy, Dept Pediat, Providence, RI 02903 USA. EM srudders@lifespan.org NR 9 TC 7 Z9 7 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2012 VL 130 IS 5 BP 1216 EP 1218 DI 10.1016/j.jaci.2012.08.029 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 030LE UT WOS:000310571400031 PM 23021879 ER PT J AU Liu, J Lee, GY Lawitts, JA Toner, M Biggers, JD AF Liu, J. Lee, G. Y. Lawitts, J. A. Toner, M. Biggers, J. D. TI Technical note: Mice produced by intracytoplasmic sperm injection using a modified conventional method SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE conventional method; injection pipette; intracytoplasmic sperm injection; mouse ID MOUSE AB A piezo-driven pipette that includes a small amount of mercury to enhance efficiency is widely used for mouse intracytoplasmic sperm injection (ICSI). Unfortunately, the use of toxic mercury is not permitted in hospital facilities and alternatives to mercury that enhance performance of the device do not work as well in the mouse. We have eliminated mercury toxicity and obtained acceptable ICSI efficiency using a modified conventional method. With this technique, oocyte survival, fertilization (number of 2-cell) and blastocyst rates were 77/126 (61.1%), 65/77 (84.4%), and 45/65 (69.2%), respectively. Eleven live pups were born from the transfer of thirty-two 2- to 4-cell embryos to 2 surrogate mothers. This conventional method is efficient, simple, and does not need the assistance of piezo-driven devices. C1 [Liu, J.; Lee, G. Y.; Toner, M.; Biggers, J. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Liu, J.; Lee, G. Y.; Toner, M.; Biggers, J. D.] Shriners Hosp Children, Boston, MA 02114 USA. [Lawitts, J. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Biggers, J. D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Liu, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM Liu.Jie@mgh.harvard.edu FU National Institutes of Health; National Center for Research Resources [NIH/NCRR 5 R24 RR018934] FX The authors thank Yunseok Heo for helping with embryo images. We also thank funding support from the National Institutes of Health and the National Center for Research Resources (NIH/NCRR 5 R24 RR018934). NR 11 TC 5 Z9 5 U1 1 U2 6 PU AMER SOC ANIMAL SCIENCE PI CHAMPAIGN PA PO BOX 7410, CHAMPAIGN, IL 61826-7410 USA SN 0021-8812 EI 1525-3163 J9 J ANIM SCI JI J. Anim. Sci. PD NOV PY 2012 VL 90 IS 11 BP 3739 EP 3742 DI 10.2527/jas.2012-5136 PG 4 WC Agriculture, Dairy & Animal Science SC Agriculture GA 036MN UT WOS:000311030500006 PM 22665678 ER PT J AU Pinne, M Matsunaga, J Haake, DA AF Pinne, Marija Matsunaga, James Haake, David A. TI Leptospiral Outer Membrane Protein Microarray, a Novel Approach to Identification of Host Ligand-Binding Proteins SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; EXTRACELLULAR-MATRIX PROTEINS; GRAM-NEGATIVE BACTERIA; STAPHYLOCOCCUS-AUREUS; BORRELIA-BURGDORFERI; IMMUNODOMINANT ANTIGENS; PATHOGEN INTERACTIONS; CAMPYLOBACTER-JEJUNI; ANTIBODY-RESPONSES; SIGNAL PEPTIDES AB Leptospirosis is a zoonosis with worldwide distribution caused by pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via freshwater and colonization of the renal tubules of their reservoir hosts. Infection requires adherence to cell surfaces and extracellular matrix components of host tissues. These host-pathogen interactions involve outer membrane proteins (OMPs) expressed on the bacterial surface. In this study, we developed an Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 OMP microarray containing all predicted lipoproteins and transmembrane OMPs. A total of 401 leptospiral genes or their fragments were transcribed and translated in vitro and printed on nitrocellulose-coated glass slides. We investigated the potential of this protein microarray to screen for interactions between leptospiral OMPs and fibronectin (Fn). This approach resulted in the identification of the recently described fibronectin-binding protein, LIC10258 (MFn8, Lsa66), and 14 novel Fn-binding proteins, denoted Microarray Fn-binding proteins (MFns). We confirmed Fn binding of purified recombinant LIC11612 (MFn1), LIC10714 (MFn2), LIC11051 (MFn6), LIC11436 (MFn7), LIC10258 (MFn8, Lsa66), and LIC10537 (MFn9) by far-Western blot assays. Moreover, we obtained specific antibodies to MFn1, MFn7, MFn8 (Lsa66), and MFn9 and demonstrated that MFn1, MFn7, and MFn9 are expressed and surface exposed under in vitro growth conditions. Further, we demonstrated that MFn1, MFn4 (LIC12631, Sph2), and MFn7 enable leptospires to bind fibronectin when expressed in the saprophyte, Leptospira biflexa. Protein microarrays are valuable tools for high-throughput identification of novel host ligand-binding proteins that have the potential to play key roles in the virulence mechanisms of pathogens. C1 [Pinne, Marija; Matsunaga, James] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Pinne, Marija; Matsunaga, James; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Pinne, M (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. EM mpinne@ucla.edu FU VA Medical Research Funds; National Institute of Allergy and Infectious Diseases [AI-034431] FX This study was supported by VA Medical Research Funds (to D.A.H. and J.M.) and grant AI-034431 (to D.A.H.) from the National Institute of Allergy and Infectious Diseases. NR 108 TC 19 Z9 19 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2012 VL 194 IS 22 BP 6074 EP 6087 DI 10.1128/JB.01119-12 PG 14 WC Microbiology SC Microbiology GA 030SB UT WOS:000310589300007 PM 22961849 ER PT J AU Huang, YY Gupta, A Vecchio, D de Arce, VJB Huang, SF Xuan, WJ Hamblin, MR AF Huang, Ying-Ying Gupta, Asheesh Vecchio, Daniela de Arce, Vida J. Bil Huang, Shih-Fong Xuan, Weijun Hamblin, Michael R. TI Transcranial low level laser (light) therapy for traumatic brain injury SO JOURNAL OF BIOPHOTONICS LA English DT Article DE Low level laser therapy; photobiomodulation; NIR laser; traumatic brain injury; stroke; mouse models; neurogenesis; clinical trials ID TERM NEUROLOGICAL DEFICITS; ACUTE ISCHEMIC-STROKE; CYTOCHROME-C-OXIDASE; NEAR-INFRARED LIGHT; NITRIC-OXIDE; EMBOLIC STROKES; UNITED-STATES; IR RADIATION; IRRADIATION; RATS AB We review the use of transcranial low-level laser (light) therapy (LLLT) as a possible treatment for traumatic-brain injury (TBI). The basic mechanisms of LLLT at the cellular and molecular level and its effects on the brain are outlined. Many interacting processes may contribute to the beneficial effects in TBI including neuroprotection, reduction of inflammation and stimulation of neurogenesis. Animal studies and clinical trials of transcranial-LLLT for ischemic stroke are summarized. Several laboratories have shown that LLLT is effective in increasing neurological performance and memory and learning in mouse models of TBI. There have been case report papers that show beneficial effects of transcranial-LLLT in a total of three patients with chronic TBI. Our laboratory has conducted three studies on LLLT and TBI in mice. One looked at pulsed-vs-continuous wave laser-irradiation and found 10 Hz to be superior. The second [GRAPHICS] looked at four different laser-wavelengths (660, 730, 810, and 980 nm); only 660 and 810 nm were effective. The last looked at different treatment repetition regimens (1, 3 and 14-daily laser-treatments). C1 [Huang, Ying-Ying; Gupta, Asheesh; Vecchio, Daniela; de Arce, Vida J. Bil; Huang, Shih-Fong; Xuan, Weijun; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying; Gupta, Asheesh; Vecchio, Daniela; Huang, Shih-Fong; Xuan, Weijun; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Gupta, Asheesh] Def Inst Physiol & Allied Sci, Delhi 110054, India. [Huang, Shih-Fong] Taipei Vet Gen Hosp, Taipei 112, Taiwan. [Xuan, Weijun] Chinese Med Univ Guangxi, Dept Otolaryngol, Nanning, Peoples R China. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research Military Photomedicine Program [FA9550-11-1-0331] FX Supported by NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research Military Photomedicine Program (FA9550-11-1-0331). NR 64 TC 21 Z9 22 U1 3 U2 18 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1864-063X J9 J BIOPHOTONICS JI J. Biophotonics PD NOV PY 2012 VL 5 IS 11-12 SI SI BP 827 EP 837 DI 10.1002/jbio.201200077 PG 11 WC Biochemical Research Methods; Biophysics; Optics SC Biochemistry & Molecular Biology; Biophysics; Optics GA 033MS UT WOS:000310801800006 PM 22807422 ER PT J AU Bayes, J Lashkari, K AF Bayes, Joseph Lashkari, Kameran TI Wiggle technique for orbital block SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Letter ID RETROBULBAR HEMORRHAGE; PERIBULBAR ANESTHESIA; COMPLICATIONS; PERFORATION; INJECTIONS; GLOBE C1 [Bayes, Joseph] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Lashkari, Kameran] Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Bayes, J (reprint author), Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. EM joseph_bayes@meei.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD NOV PY 2012 VL 24 IS 7 BP 599 EP 600 DI 10.1016/j.jclinane.2011.10.018 PG 2 WC Anesthesiology SC Anesthesiology GA 032LH UT WOS:000310719600017 PM 23101779 ER PT J AU Kee, Y D'Andrea, AD AF Kee, Younghoon D'Andrea, Alan D. TI Molecular pathogenesis and clinical management of Fanconi anemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CROSS-LINK REPAIR; HEMATOPOIETIC-CELL TRANSPLANTATION; DAMAGE RESPONSE PATHWAY; PLURIPOTENT STEM-CELLS; ACUTE MYELOID-LEUKEMIA; NATURAL GENE-THERAPY; CORE-COMPLEX PROTEIN; DNA-REPAIR; MONOUBIQUITINATED FANCD2; HOMOLOGOUS RECOMBINATION AB Fanconi anemia (FA) is a rare genetic disorder associated with a high frequency of hematological abnormalities and congenital anomalies. Based on multilateral efforts from basic scientists and clinicians, significant advances in our knowledge of FA have been made in recent years. Here we review the clinical features, the diagnostic criteria, and the current and future therapies of FA and describe the current understanding of the molecular basis of the disease. C1 [Kee, Younghoon] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA. [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol & Pediat, Boston, MA 02115 USA. RP Kee, Y (reprint author), Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, 216 Biosci Facil Bldg, Tampa, FL 33620 USA. EM ykee@usf.edu; alan_dandrea@dfci.harvard.edu FU NIH [R01DK43889, R37HL52725, 2P01HL048546] FX We apologize for those whose work is not cited due to space limitations. We thank Alexandra Feinstein for critical reading of the manuscript. This work was supported by NIH grants R01DK43889, R37HL52725, and 2P01HL048546 to A.D. D'Andrea and by departmental startup funds to Y. Kee. NR 118 TC 103 Z9 105 U1 0 U2 20 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 3799 EP 3806 DI 10.1172/JCI58321 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600002 PM 23114602 ER PT J AU Soto-Gutierrez, A Wertheim, JA Ott, HC Gilbert, TW AF Soto-Gutierrez, Alejandro Wertheim, Jason A. Ott, Harald C. Gilbert, Thomas W. TI Perspectives on whole-organ assembly: moving toward transplantation on demand SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PLURIPOTENT STEM-CELLS; SMALL-INTESTINAL SUBMUCOSA; EXTRACELLULAR-MATRIX SCAFFOLDS; 3-DIMENSIONAL COLLAGEN MATRIX; IN-VITRO; REGENERATIVE MEDICINE; GENE-EXPRESSION; HEPATOCYTE TRANSPLANTATION; TISSUE ARCHITECTURE; ENDOTHELIAL-CELLS AB There is an ever-growing demand for transplantable organs to replace acute and chronically damaged tissues. This demand cannot be met by the currently available donor organs. Efforts to provide an alternative source have led to the development of organ engineering, a discipline that combines cell biology, tissue engineering, and cell/organ transplantation. Over the last several years, engineered organs have been implanted into rodent recipients and have shown modest function. In this article, we summarize the most recent advances in this field and provide a perspective on the challenges of translating this promising new technology into a proven regenerative therapy. C1 [Soto-Gutierrez, Alejandro] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15201 USA. [Soto-Gutierrez, Alejandro] Univ Pittsburgh, Ctr Innovat Regenerat Therapies, Pittsburgh, PA 15201 USA. [Soto-Gutierrez, Alejandro] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Surg, Transplantat Sect, Pittsburgh, PA 15201 USA. [Gilbert, Thomas W.] Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Surg, Pittsburgh, PA 15201 USA. [Soto-Gutierrez, Alejandro] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA 15201 USA. [Wertheim, Jason A.] Northwestern Univ, Comprehens Transplant Ctr, Chicago, IL 60611 USA. [Wertheim, Jason A.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Wertheim, Jason A.] Northwestern Univ, Inst BioNanotechnol Med, Chicago, IL 60611 USA. [Wertheim, Jason A.] Northwestern Univ, Chem Life Processes Inst, Evanston, IL USA. [Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Boston, MA USA. [Gilbert, Thomas W.] Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Cardiothorac Surg, Pittsburgh, PA 15201 USA. [Gilbert, Thomas W.] Univ Pittsburgh, McGowan Inst Regenerat Med, Dept Bioengn, Pittsburgh, PA 15201 USA. RP Soto-Gutierrez, A (reprint author), Univ Pittsburgh, Dept Pathol, 3511 Rangos Res Bldg,530 45th St, Pittsburgh, PA 15201 USA. EM sotogutierreza@upmc.edu; jwerthei@nmh.org; hott@partners.org; thomasgilbert@acell.com RI Wertheim, Jason/H-1275-2014 OI Wertheim, Jason/0000-0001-5680-1067 FU NIH [DK083556, EB009237, DC009655]; American Society of Transplantation; Excellence in Academic Medicine Act through the Illinois Department of Healthcare and Family Services; Northwestern Memorial Foundation Dixon Translational Research Grants Initiative; Zell Family Foundation; American Association for the Study of Liver Diseases; American Liver Foundation Liver Scholar Award; Health Resources and Services Administration [234-2005-37011C] FX We acknowledge the support of the NIH (DK083556 to A. Soto-Gutierrez; EB009237 and DC009655 to T.W. Gilbert). This work was also supported by a faculty development grant from the American Society of Transplantation to A. Soto-Gutierrez and the Excellence in Academic Medicine Act through the Illinois Department of Healthcare and Family Services, the Northwestern Memorial Foundation Dixon Translational Research Grants Initiative, a grant from the Zell Family Foundation, the American Association for the Study of Liver Diseases, and the American Liver Foundation Liver Scholar Award to J.A. Wertheim. We also would like to thank Ken Fukumitsu for his critical comments on this manuscript. This work was supported in part by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 122 TC 45 Z9 47 U1 1 U2 26 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 3817 EP 3823 DI 10.1172/JCI61974 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600004 PM 23114604 ER PT J AU Ferris, HA Kahn, CR AF Ferris, Heather A. Kahn, C. Ronald TI New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID DEXAMETHASONE-TREATED RATS; GENE-EXPRESSION; OSTEOCALCIN; MICE; METABOLISM; RECEPTOR; MUSCLE; LIVER; FAT AB Glucocorticoids are a powerful tool used to treat a range of human illnesses, including autoimmune diseases and cancer, and to prevent rejection following organ transplantation. While lifesaving for many, they come with a steep price, often leading to obesity, insulin resistance, diabetes, and osteoporosis. In this issue of the JCI, Brennan-Speranza and colleagues provide evidence that the osteoblast-derived peptide osteocalcin is one of the drivers of the metabolic derangements associated with glucocorticoid therapy. This novel mechanism could open up new avenues for the treatment of these disorders. C1 [Ferris, Heather A.; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu NR 22 TC 33 Z9 34 U1 0 U2 15 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 3854 EP 3857 DI 10.1172/JCI66180 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600014 PM 23093783 ER PT J AU Russo, SB Baicu, CF Van Laer, A Geng, TY Kasiganesan, H Zile, MR Cowart, LA AF Russo, Sarah Brice Baicu, Catalin F. Van Laer, An Geng, Tuoyu Kasiganesan, Harinath Zile, Michael R. Cowart, L. Ashley TI Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MONOUNSATURATED FATTY-ACIDS; INDUCED INSULIN-RESISTANCE; BETA-CELL TURNOVER; CARDIAC-HYPERTROPHY; HEART-FAILURE; CHAIN-LENGTH; DIABETIC CARDIOMYOPATHY; SUBSTRATE-SPECIFICITY; HEMODYNAMIC STRESS; METABOLIC SYNDROME AB Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demonstrated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy. C1 [Russo, Sarah Brice; Geng, Tuoyu; Cowart, L. Ashley] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Baicu, Catalin F.; Van Laer, An; Kasiganesan, Harinath; Zile, Michael R.] Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29403 USA. [Zile, Michael R.; Cowart, L. Ashley] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Cowart, LA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 114 Doughty St,Strom Thurmond Bldg,Rm 423, Charleston, SC 29403 USA. EM cowartl@musc.edu FU Cancer Center Support Grant [P30 CA138313]; COBRE in Lipidomics in Pathobiology [NIH P20RR017077]; National Institute of Diabetes and Digestive and Kidney Diseases [F30DK092125]; Department of Veterans Affairs; NIH COBRE in Lipidomics and Pathobiology at MUSC FX We thank Donald Menick for his invaluable support of this project in its early stages; Benjamin Addy and Santhosh Mani for cell culture and technical assistance; Wei Hu for technical assistance; and Yusuf Hannun for helpful comments. Imaging studies were performed using the Cell and Molecular Imaging Shared Resource (supported in part by Cancer Center Support Grant P30 CA138313 to the Hollings Cancer Center at MUSC), with help from Venkat Ramshesh. LC/MS lipid measurements were performed at the Lipidomics Core Facility at MUSC, which is supported by the COBRE in Lipidomics in Pathobiology (NIH P20RR017077). Support for this work was provided by grant number F30DK092125 from the National Institute of Diabetes and Digestive and Kidney Diseases (to S.B. Russo), merit awards from the Department of Veterans Affairs (to L.A. Cowart and M.R. Zile), and the NIH COBRE in Lipidomics and Pathobiology at MUSC (to L.A. Cowart). NR 77 TC 61 Z9 62 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 3919 EP 3930 DI 10.1172/JCI63888 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600022 PM 23023704 ER PT J AU Mallick, EM McBee, ME Vanguri, VK Melton-Celsa, AR Schlieper, K Karalius, BJ O'Brien, AD Butterton, JR Leong, JM Schauer, DB AF Mallick, Emily M. McBee, Megan E. Vanguri, Vijay K. Melton-Celsa, Angela R. Schlieper, Katherine Karalius, Brad J. O'Brien, Alison D. Butterton, Joan R. Leong, John M. Schauer, David B. TI A novel murine infection model for Shiga toxin-producing Escherichia coli SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CITROBACTER-FREUNDII BIOTYPE; GERM-FREE MICE; COLONIC HYPERPLASIA; MOUSE MODEL; KIDNEY INJURY; BACTERIOPHAGE-LAMBDA; RENAL INFLAMMATION AB Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates "attaching and effacing" (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease. C1 [Leong, John M.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Mallick, Emily M.; Leong, John M.] Univ Massachusetts, Sch Med, Dept Microbiol & Physiol Syst, Worcester, MA USA. [McBee, Megan E.; Schlieper, Katherine; Schauer, David B.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Vanguri, Vijay K.] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. [Melton-Celsa, Angela R.; O'Brien, Alison D.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Schlieper, Katherine; Schauer, David B.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Karalius, Brad J.; Butterton, Joan R.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Leong, JM (reprint author), Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, 136 Harrison Ave, Boston, MA 02111 USA. EM john.leong@rufts.edu OI O'Brien, Alison/0000-0002-1315-3204 FU NIH [R21 AI92009, R01 AI46454, R37 AI20148, R01 049842, R01 AI049842, 026731 PHS P01CA026731]; NIH/New England Regional Center for Excellence, Biodefense and Emerging Infectious Diseases Cooperative Pilot Projects Program [R01 DK59101] FX We thank the UMass Diabetes and Endocrinology Research Center facility for fixing, sectioning, and staining all tissue sections and particularly Lara Strittmatter and Gregory Hendricks of the UMass Electron Microscopy Core Facility for the invaluable electron microscopy work. The UMass Mouse Phenotyping Core Facility performed Luminex cytokine and blood chemistry studies. This work was supported by NIH R21 AI92009 and R01 AI46454 to J.M. Leong; R37 AI20148 to A. O'Brien; R01 049842, R01 AI049842, and 026731 PHS P01CA026731 to D.B. Schauer; and NIH/New England Regional Center for Excellence, Biodefense and Emerging Infectious Diseases Cooperative Pilot Projects Program R01 DK59101 to J.R. Butterton and D.B. Schauer. NR 122 TC 19 Z9 19 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 4012 EP 4024 DI 10.1172/JCI62746 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600031 PM 23041631 ER PT J AU Lee, RJ Xiong, GX Kofonow, JM Chen, B Lysenko, A Jiang, PH Abraham, V Doghramji, L Adappa, ND Palmer, JN Kennedy, DW Beauchamp, GK Doulias, PT Ischiropoulos, H Kreindler, JL Reed, DR Cohen, NA AF Lee, Robert J. Xiong, Guoxiang Kofonow, Jennifer M. Chen, Bei Lysenko, Anna Jiang, Peihua Abraham, Valsamma Doghramji, Laurel Adappa, Nithin D. Palmer, James N. Kennedy, David W. Beauchamp, Gary K. Doulias, Paschalis-Thomas Ischiropoulos, Harry Kreindler, James L. Reed, Danielle R. Cohen, Noam A. TI T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CILIARY BEAT FREQUENCY; BRONCHIAL EPITHELIAL-CELLS; HUMAN AIRWAY EPITHELIA; PSEUDOMONAS-AERUGINOSA; NITRIC-OXIDE; CHRONIC RHINOSINUSITIS; INTRACELLULAR CALCIUM; BURKHOLDERIA-CEPACIA; IN-VITRO; INDIVIDUAL-DIFFERENCES AB Innate and adaptive defense mechanisms protect the respiratory system from attack by microbes. Here, we present evidence that the bitter taste receptor T2R38 regulates the mucosal innate defense of the human upper airway. Utilizing immunofluorescent and live cell imaging techniques in polarized primary human sinonasal cells, we demonstrate that T2R38 is expressed in human upper respiratory epithelium and is activated in response to acyl-homoserine lactone quorum-sensing molecules secreted by Pseudomonas aeruginosa and other gram-negative bacteria. Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance and direct antibacterial effects. Moreover, common polymorphisms of the TAS2R38 gene were linked to significant differences in the ability of upper respiratory cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation contributes to individual differences in susceptibility to respiratory infection. C1 [Lee, Robert J.; Kofonow, Jennifer M.; Chen, Bei; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Xiong, Guoxiang] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA USA. [Lysenko, Anna; Jiang, Peihua; Beauchamp, Gary K.; Reed, Danielle R.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Abraham, Valsamma; Doulias, Paschalis-Thomas; Ischiropoulos, Harry; Kreindler, James L.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA. [Doulias, Paschalis-Thomas; Ischiropoulos, Harry] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. RP Cohen, NA (reprint author), Hosp Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Ravdin Bldg 5th Floor,3400 Spruce St, Philadelphia, PA 19004 USA. EM cohenn@uphs.upenn.edu RI Doulias, Paschalis-Thomas/I-7318-2013; OI Cohen, Noam/0000-0002-9462-3932; Reed, Danielle/0000-0002-4374-6107; Lee, Robert/0000-0001-5826-6686 FU Flight Attendants Medical Research Institute [082478]; USPHS [P30DC011735, R01DC004698, P50DC000214, R01DC010842] FX We thank D.M. Sabatini, P.F. Worley, A.S. Cohen, N.M. Cohen, J.C. Saunders, and Y.E. Cohen for critical reading of this manuscript. We also thank B.H. Igelwski and J.M. Schwingel for Pseudomonas strain PAO-JP2, G. O'Toole for Pseudomonas strain Sad36, and D. LaRosa for FLS-1. This work was supported by a grant from the Flight Attendants Medical Research Institute 082478 (to N.A. Cohen), a philanthropic contribution from the RLG Foundation Inc. (to N.A. Cohen), and USPHS grants P30DC011735 (to D.R. Reed), R01DC004698 (to D.R. Reed), P50DC000214 (to G.K. Beauchamp), and R01DC010842 (to P. Jiang). NR 93 TC 135 Z9 136 U1 4 U2 46 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2012 VL 122 IS 11 BP 4145 EP 4159 DI 10.1172/JCI64240 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 031WP UT WOS:000310673600041 PM 23041624 ER PT J AU Mayer, EL Lin, NU AF Mayer, Erica L. Lin, Nancy U. TI Long Term Follow-Up of National Surgical Adjuvant Breast and Bowel Project Trial B-31: How Well Can We Predict Cardiac Toxicity With Trastuzumab? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION; HIGH-DOSE CHEMOTHERAPY; INDUCED CARDIOTOXICITY; CANCER; SAFETY; ANTHRACYCLINES; EFFICACY; WOMEN; PLUS C1 [Mayer, Erica L.; Lin, Nancy U.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. RP Mayer, EL (reprint author), Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 31 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2012 VL 30 IS 31 BP 3769 EP 3772 DI 10.1200/JCO.2012.44.9611 PG 4 WC Oncology SC Oncology GA 030PT UT WOS:000310583300007 PM 22987088 ER PT J AU Cruciani, RA Zhang, JJ Manola, J Cella, D Ansari, B Fisch, MJ AF Cruciani, Ricardo A. Zhang, Jenny J. Manola, Judith Cella, David Ansari, Bilal Fisch, Michael J. TI L-Carnitine Supplementation for the Management of Fatigue in Patients With Cancer: An Eastern Cooperative Oncology Group Phase III, Randomized, Double-Blind, Placebo-Controlled Trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIAL; DEFICIENCY; PROFILES; LIFE AB Purpose L-carnitine, a popular complementary and alternative medicine product, is used by patients with cancer for the treatment of fatigue, the most commonly reported symptom in this patient population. The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer. Patients and Methods In this double-blind, placebo-controlled trial, patients with invasive malignancies and fatigue were randomly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo. The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory (BFI). Results Three hundred seventy-six patients were randomly assigned to treatment with L-carnitine supplementation or placebo. L-carnitine supplementation resulted in significant carnitine plasma level increase by week 4. The primary outcome, fatigue, measured using the BFI, improved in both arms compared with baseline (L-carnitine: -0.96, 95% CI, -1.32 to -0.60; placebo: -1.11, 95% CI -1.44 to -0.78). There were no statistically significant differences between arms (P = .57). Secondary outcomes, including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument, depression, and pain, did not show significant difference between arms. A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation. Conclusion Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status. J Clin Oncol 30: 3864-3869. (C) 2012 by American Society of Clinical Oncology C1 [Cruciani, Ricardo A.] Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. [Cruciani, Ricardo A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Manola, Judith] Dana Farber Canc Inst, Eastern Cooperat Oncol Grp, Stat Off, Boston, MA 02115 USA. [Cella, David] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Ansari, Bilal] Mem Hosp S Bend, South Bend, IN USA. [Fisch, Michael J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zhang, Jenny J.] US FDA, Silver Spring, MD USA. RP Cruciani, RA (reprint author), Beth Israel Deaconess Med Ctr, Dept Pain Med & Palliat Care, New York, NY 10003 USA. EM rcruciani@chpnet.org FU National Cancer Institute, US Department of Health and Human Services [CA-23318] FX Supported by Grant No. CA-23318, National Cancer Institute, US Department of Health and Human Services. NR 16 TC 26 Z9 27 U1 0 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2012 VL 30 IS 31 BP 3864 EP 3869 DI 10.1200/JCO.2011.40.2180 PG 6 WC Oncology SC Oncology GA 030PT UT WOS:000310583300023 PM 22987089 ER PT J AU Tejera, P Meyer, NJ Chen, F Feng, R Zhao, Y O'Mahony, DS Li, L Sheu, CC Zhai, RH Wang, ZX Su, L Bajwa, E Ahasic, AM Clardy, PF Gong, MN Frank, AJ Lanken, PN Thompson, BT Christie, JD Wurfel, MM O'Keefe, GE Christiani, DC AF Tejera, Paula Meyer, Nuala J. Chen, Feng Feng, Rui Zhao, Yang O'Mahony, D. Shane Li, Lin Sheu, Chau-Chyun Zhai, Rihong Wang, Zhaoxi Su, Li Bajwa, Ed Ahasic, Amy M. Clardy, Peter F. Gong, Michelle N. Frank, Angela J. Lanken, Paul N. Thompson, B. Taylor Christie, Jason D. Wurfel, Mark M. O'Keefe, Grant E. Christiani, David C. TI Distinct and replicable genetic risk factors for acute respiratory distress syndrome of pulmonary or extrapulmonary origin SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ACUTE LUNG INJURY; GENOME-WIDE ASSOCIATION; ACID AMIDE HYDROLASE; EUROPEAN CONSENSUS CONFERENCE; TIDAL VOLUME VENTILATION; BODY-MASS INDEX; POPULATION STRATIFICATION; ENDOCANNABINOID SYSTEM; RECRUITMENT MANEUVER; CLINICAL-USE AB Background The role of genetics in the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) from direct or indirect lung injury has not been specifically investigated. The aim of this study was to identify genetic variants contributing to ALI/ARDS from pulmonary or extrapulmonary causes. Methods We conducted a multistage genetic association study. We first performed a large-scale genotyping (50K ITMAT-Broad_CARe Chip) in 1717 critically ill Caucasian patients with either pulmonary or extrapulmonary injury, to identify single nucleotide polymorphisms (SNPs) associated with the development of ARDS from direct or indirect insults to the lung. Identified SNPs (p=0.0005) were validated in two separated populations (Stage II), with trauma (Population I; n=765) and pneumonia/pulmonary sepsis (Population II; n=838), as causes for ALI/ARDS. Genetic variants replicating their association with trauma related-ALI in Stage II were validated in a second trauma-associated ALI population (n=224, Stage III). Results In Stage I, non-overlapping SNPs were significantly associated with ARDS from direct/indirect lung injury, respectively. The association between rs1190286 (POPDC3) and reduced risk of ARDS from pulmonary injury was validated in Stage II (p<0.003). SNP rs324420 (FAAH) was consistently associated with increased risk of ARDS from extrapulmonary causes in two independent ALI-trauma populations (p<0.006, Stage II; p<0.05, Stage III). Meta-analysis confirmed these associations. Conclusions Different genetic variants may influence ARDS susceptibility depending on direct versus indirect insults. Functional SNPs in POPDC3 and FAAH genes may be driving the association with direct and indirect ALI/ARDS, respectively. C1 [Tejera, Paula; Zhao, Yang; Li, Lin; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Meyer, Nuala J.; Lanken, Paul N.; Christie, Jason D.] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Chen, Feng] Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing, Jiangsu, Peoples R China. [Feng, Rui; Christie, Jason D.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [O'Mahony, D. Shane; Wurfel, Mark M.; O'Keefe, Grant E.] Univ Washington, Harborview Med Ctr, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98104 USA. [Sheu, Chau-Chyun] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Div Pulm & Crit Care Med, Kaohsiung, Taiwan. [Bajwa, Ed; Frank, Angela J.; Thompson, B. Taylor; Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. [Ahasic, Amy M.] Yale Univ, Sch Med, Dept Med, Sect Pulm & Crit Care Med,Anlyan Ctr, New Haven, CT 06510 USA. [Clardy, Peter F.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr BIDMC, Div Pulm Crit Care & Sleep Med, Boston, MA USA. [Gong, Michelle N.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Dept Med, Div Crit Care Med,Montefiore Med Ctr, Bronx, NY 10467 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,Room 1-1401, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu FU National Institute of Health [HL060710, ES00002, GM066946, P01-HL079063, P50-HL60290]; grant CajaMadrid (Spain) FX This work was supported by National Institute of Health (HL060710, ES00002, GM066946, P01-HL079063, P50-HL60290). Dr Tejera was supported by grant CajaMadrid (Spain). NR 70 TC 17 Z9 17 U1 0 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2012 VL 49 IS 11 BP 671 EP 680 DI 10.1136/jmedgenet-2012-100972 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 031IN UT WOS:000310632800002 PM 23048207 ER PT J AU Gros, DF Magruder, KM Ruggiero, KJ Shaftman, SR Frueh, BC AF Gros, Daniel F. Magruder, Kathryn M. Ruggiero, Kenneth J. Shaftman, Stephanie R. Frueh, B. Christopher TI Comparing the Symptoms of Posttraumatic Stress Disorder With the Distress and Fear Disorders SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; anxiety disorders; depressive disorders; comorbidity; transdiagnostic ID PRIMARY-CARE CLINICS; ADMINISTERED PTSD SCALE; VA PRIMARY-CARE; PSYCHOMETRIC PROPERTIES; ANXIETY DISORDERS; DSM-IV; MOOD DISORDERS; VETERANS; COMORBIDITY; PREVALENCE AB New theoretical models of mood and anxiety disorders have been proposed to better understand the relations and patterns leading to their high diagnostic comorbidities. These models have highlighted two new groupings of the disorders, focused on the prevalence of fear and distress symptoms. The present study investigated the fit of the symptoms of posttraumatic stress disorder (PTSD) in these new models. The relations between the two primary sets of symptom scales of PTSD and the diagnoses of other comorbid disorders were examined in a large multisite sample of veterans from primary care clinics. The results suggested that there was no reliable difference in the predictive power of any of the PTSD symptom scales across the two diagnostic groups. New transdiagnostic models, assessment practices, and treatment approaches may provide better understanding of symptom overlap and diagnostic comorbidity in PTSD and related disorders. C1 [Gros, Daniel F.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. [Gros, Daniel F.; Magruder, Kathryn M.; Ruggiero, Kenneth J.; Shaftman, Stephanie R.] Med Univ S Carolina, Charleston, SC 29425 USA. [Frueh, B. Christopher] Menninger Clin, Houston, TX USA. [Frueh, B. Christopher] Univ Hawaii, Hilo, HI 96720 USA. RP Gros, DF (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. EM grosd@musc.edu FU Veterans Affairs Health Services Research and Development [VCR-99-010-2] FX This study was partially supported by grant VCR-99-010-2 from Veterans Affairs Health Services Research and Development. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the US government. NR 49 TC 4 Z9 4 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2012 VL 200 IS 11 BP 967 EP 972 DI 10.1097/NMD.0b013e3182718a36 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 033KN UT WOS:000310794900010 PM 23124181 ER PT J AU Hirsch, JA Albuquerque, FC Fiorella, D Prestigiacomo, CJ Zaidat, O Tarr, RW AF Hirsch, Joshua A. Albuquerque, Felipe C. Fiorella, David Prestigiacomo, Charles J. Zaidat, Osama Tarr, Robert W. TI JNIS: factoring the impact SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Editorial Material ID ENDOVASCULAR TREATMENT; ISCHEMIC-STROKE; MALFORMATIONS; PROTECTION; ANEURYSMS; DEVICE C1 [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA. [Albuquerque, Felipe C.] Barrow Neurol Inst, Div Neurol Surg, Phoenix, AZ 85013 USA. [Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY 11794 USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. [Zaidat, Osama] Med Coll Wisconsin, Dept Neurol Neurosurg & Radiol, Milwaukee, WI 53226 USA. [Tarr, Robert W.] Univ Hosp Case Med Ctr, Dept Radiol, Cincinnati, OH USA. RP Hirsch, JA (reprint author), Massachusetts Gen Hosp, NeuroEndovasc Program, 55 Fruit St,Gray 241B, Boston, MA 02114 USA. EM hirsch@snisonline.org NR 20 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD NOV PY 2012 VL 4 IS 6 BP 395 EP 396 DI 10.1136/neurintsurg-2012-010526 PG 2 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 029MX UT WOS:000310501000011 PM 23042935 ER PT J AU Hussain, MS Fraser, JF Abruzzo, T Blackham, KA Bulsara, KR Derdeyn, CP Gandhi, CD Hirsch, JA Hsu, DP Jayaraman, MV Meyers, PM Narayanan, S Prestigiacomo, CJ Rasmussen, PA AF Hussain, M. Shazam Fraser, Justin F. Abruzzo, Todd Blackham, Kristine A. Bulsara, Ketan R. Derdeyn, Colin P. Gandhi, Chirag D. Hirsch, Joshua A. Hsu, Daniel P. Jayaraman, Mahesh V. Meyers, Philip M. Narayanan, Sandra Prestigiacomo, Charles J. Rasmussen, Peter A. CA Soc NeuroInterventional Surg TI Standard of practice: endovascular treatment of intracranial atherosclerosis SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID MIDDLE CEREBRAL-ARTERY; STENT-ASSISTED ANGIOPLASTY; MAGNETIC-RESONANCE ANGIOGRAPHY; TRANSIENT ISCHEMIC ATTACK; DRUG-ELUTING STENTS; TERM-FOLLOW-UP; CLINICAL-PRACTICE GUIDELINES; NORTHERN MANHATTAN STROKE; HIGH-RISK PATIENTS; INITIAL-EXPERIENCE AB Background Symptomatic intracranial atherosclerotic disease (ICAD) worldwide represents one of the most prevalent causes of stroke. When severe, studies show that it has a very high risk for recurrent stroke, highlighting the need for effective preventative strategies. The mainstay of treatment has been medical therapy and is of critical importance in all patients with this disease. Endovascular therapy is also a possible therapeutic option but much remains to be defined in terms of best techniques and patient selection. This guideline will serve as recommendations for diagnosis and endovascular treatment of patients with ICAD. Methods A literature review was performed to extract published literature regarding ICAD, published from 2000 to 2011. Evidence was evaluated and classified according to American Heart Association (AHA)/American Stroke Association standard. Recommendations are made based on available evidence assessed by the Standards Committee of the Society of NeuroInterventional Surgery. The assessment was based on guidelines for evidence based medicine proposed by the American Academy of Neurology (AAN), the Stroke Council of the AHA and the University of Oxford, Centre for Evidence Based Medicine (CEBM). Results 59 publications were identified. The SAMMPRIS study is the only prospective, randomized, controlled trial available and is given an AHA level B designation, AAN class II and CEBM level 1b. The Stenting of Symptomatic Atherosclerotic Lesions in the Vertebral or Intracranial arteries (SSYLVIA) trial was a prospective, non-randomized study with the outcome assessment made by a non-operator study neurologist, allowing an AHA level B, AAN class III and CEBM level 2. The remaining studies were uncontrolled or did not have objective outcome measurement, and are thus classified as AHA level C, AAN class IV and CEBM level 4. Conclusion Medical management with combination aspirin and clopidogrel for 3 months and aggressive risk factor modification is the firstline therapy for patients with symptomatic ICAD. Endovascular angioplasty with or without stenting is a possible therapeutic option for selected patients with symptomatic ICAD. Further studies are necessary to define appropriate patient selection and the best therapeutic approach for various subsets of patients. C1 [Hussain, M. Shazam; Rasmussen, Peter A.] Cleveland Clin, Cerebrovasc Ctr, Cleveland, OH 44195 USA. [Fraser, Justin F.] Univ Kentucky, Dept Neurol Surg, Lexington, KY USA. [Abruzzo, Todd] Univ Cincinnati, Mayfield Clin, Cincinnati, OH USA. [Abruzzo, Todd] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Blackham, Kristine A.] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Radiol, Cleveland, OH 44106 USA. [Bulsara, Ketan R.] Yale Univ, Yale Dept Neurosurg, New Haven, CT USA. [Derdeyn, Colin P.] Washington Univ, Sch Med, Barnes Jewish Hosp, St Louis, MO USA. [Gandhi, Chirag D.] Univ Med & Dent New Jersey, New Jersey Med Sch, Neurol Inst New Jersey, Newark, NJ 07103 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Hsu, Daniel P.] Univ Hosp Case Med Ctr, Div Intervent Neuroradiol, Cleveland, OH USA. [Jayaraman, Mahesh V.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch, Providence, RI 02903 USA. [Meyers, Philip M.] Columbia Univ Coll Phys & Surg, Dept Radiol & Neurol Surg, New York, NY 10032 USA. [Meyers, Philip M.] Neurol Inst New York, Neuroendovasc Serv, New York, NY USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Narayanan, Sandra] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Prestigiacomo, Charles J.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol Surg, Newark, NJ 07103 USA. RP Hussain, MS (reprint author), Cleveland Clin, Cerebrovasc Ctr, 9500 Euclid Ave,S80, Cleveland, OH 44195 USA. EM hussais4@ccf.org OI Fraser, Justin/0000-0002-5980-3989; Derdeyn, Colin/0000-0002-5932-2683 NR 118 TC 10 Z9 11 U1 0 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD NOV PY 2012 VL 4 IS 6 BP 397 EP 406 DI 10.1136/neurintsurg-2012-010405 PG 10 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 029MX UT WOS:000310501000012 PM 22705876 ER PT J AU Almandoz, JED Kelly, HR Schaefer, PW Brouwers, HB Yoo, AJ Stone, MJ Goldstein, JN Rosand, J Lev, MH Gonzalez, RG Romero, JM AF Almandoz, Josser E. Delgado Kelly, Hillary R. Schaefer, Pamela W. Brouwers, H. Bart Yoo, Albert J. Stone, Michael J. Goldstein, Joshua N. Rosand, Jonathan Lev, Michael H. Gonzalez, R. Gilberto Romero, Javier M. TI CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Article ID HEMATOMA EXPANSION; CONTRAST EXTRAVASATION; IDENTIFIES PATIENTS; HIGHEST RISK; SCORE AB Background and objective The presence of active contrast extravasation during CT angiography, the spot sign, is a potent predictor of in-hospital mortality in patients with primary intracerebral hemorrhage (ICH). However, its predictive value in patients with ICH due to a vascular abnormality, secondary ICH (SICH), is unknown. The aim of this study was to determine the clinical and radiological predictors of a spot sign and in-hospital mortality in patients with SICH. Methods Two experienced readers independently reviewed CT angiograms performed on 215 consecutive patients presenting to the emergency department with SICH over a 10-year period to assess the presence of spot signs according to strict radiological criteria. Differences in reader interpretation were resolved by consensus. Medical records were reviewed for baseline clinical characteristics and in-hospital mortality. Univariate and multivariate logistic regression analyses were performed to determine the clinical and radiological predictors of a spot sign and in-hospital mortality in patients with SICH. Results Spot signs were identified in 31 of 215 patients with SICH (14.4%), four of which were delayed spot signs (12.9%). Spot signs were most common in patients with arteriovenous fistulas (42%), Moyamoya (40%), elevated admission blood glucose (23%) and large intraventricular hemorrhage volumes (29%). Spot signs were most predictive of in-hospital mortality in patients with aneurysms of the anterior cerebral artery (100%) and anterior communicating artery (75%). In univariate analysis, the presence of a spot sign significantly increased the risk of in-hospital mortality in patients with SICH (38.7%, OR 2.2, 95% CI 1.0 to 4.9, p=0.0497). However, in multivariate logistic regression analysis the admission Glasgow Coma Scale was the only independent predictor of in-hospital mortality in patients with SICH (OR 2.8, 95% CI 1.6 to 5.1, p=0.0004). Conclusion The spot sign identifies patients with SICH at increased risk of in-hospital mortality. However, the admission Glasgow Coma Scale was the only independent predictor of in-hospital mortality in this cohort of patients with SICH. C1 [Almandoz, Josser E. Delgado] Abbott NW Hosp, Minneapolis, MN 55407 USA. [Kelly, Hillary R.; Schaefer, Pamela W.; Stone, Michael J.; Lev, Michael H.; Gonzalez, R. Gilberto; Romero, Javier M.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Brouwers, H. Bart; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Almandoz, JED (reprint author), Abbott NW Hosp, Minneapolis, MN 55407 USA. EM josser.delgado@crlmed.com RI Goldstein, Joshua/H-8953-2016 FU American Heart Association [0755984T]; National Institute of Neurological Disorders and Stroke [K23NS059774] FX Funding American Heart Association Grant-in-Aid #0755984T and the National Institute of Neurological Disorders and Stroke grant #K23NS059774. NR 12 TC 10 Z9 10 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD NOV PY 2012 VL 4 IS 6 BP 442 EP 447 DI 10.1136/neurintsurg-2011-010061 PG 6 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 029MX UT WOS:000310501000018 ER PT J AU Manchikanti, L Hirsch, JA Barr, RM Donovan, WD Nicola, GN AF Manchikanti, Laxmaiah Hirsch, Joshua A. Barr, Robert M. Donovan, William D. Nicola, Greg N. TI Physician payment outlook for 2012 SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID AFFORDABLE CARE ACT; INTERVENTIONAL PAIN MANAGEMENT; OUTCOMES RESEARCH-INSTITUTE; PATIENT PROTECTION; EVOLUTION; IMPACT; PRIMER AB Physician spending is complex and intrinsically related to national health care spending, government regulations, health care reform, private insurers, physician practice and patient utilization patterns. Consequently, since the inception of Medicare programs in 1965, several methods have been used to determine the amounts paid to physicians for each covered service. The sustainable growth rate (SGR) was enacted in 1997 to determine physician payment updates under Medicare part B with an intent to reduce Medicare physician payment updates to offset the growth and utilization of physician services that exceeds the gross domestic product growth. This is achieved by setting an overall target amount of spending for physicians' services and adjusting payment rates annually to reflect differences between actual spending and the spending target. Since 2002, the SGR has annually recommended reductions in Medicare reimbursements. Payments were cut by 4.8% in 2002. Since then, Congress has intervened on 13 separate occasions to prevent additional cuts from being imposed. This manuscript describes certain important aspects of the 2012 physician fee schedule. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Barr, Robert M.] Mecklenburg Radiol Associates PA, Charlotte, NC USA. [Donovan, William D.] William W Backus Hosp, Norwich, CT USA. [Nicola, Greg N.] Hackensack Univ, Med Ctr, Dept Radiol, Hackensack, NJ USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com OI Barr, Robert/0000-0002-9214-9448 NR 14 TC 6 Z9 6 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD NOV PY 2012 VL 4 IS 6 BP 463 EP 467 DI 10.1136/neurintsurg-2012-010407 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 029MX UT WOS:000310501000022 PM 22717919 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI The Independent Payment Advisory Board: impact on neurointerventionalists SO JOURNAL OF NEUROINTERVENTIONAL SURGERY LA English DT Review ID REFORM AB The Independent Payment Advisory Board (IPAB) is a powerful component of the Affordable Care Act, with the authority to issue recommendations to reduce the growth in Medicare spending and to provide recommendations to Congress for fast-track implementation. The IPAB works by recommending policies to Congress to help Medicare provide better care at a lower cost, including ideas on coordinating care, getting rid of waste in the system, providing incentives for best practices and prioritizing primary care. Congress then has the power to accept or reject these recommendations. However, Congress faces extreme limitations either to enact policies that achieve equivalent savings or to let the Secretary of Health and Human Services (HHS) follow the IPAB's recommendations. The IPAB statute sets target growth rates for Medicare spending. The applicable percentage for maximum savings appears to be 0.5% for 2015, 1% for 2016, 1.25% for 2017 and 1.5% for 2018 and later. The IPAB Medicare proposal process involves mandatory recommendations and advisory recommendations with multiple reporting requirements. We believe neurointerventionalists, as highly specialized physicians reliant on expensive technology, should be aware of the IPAB and its impact on the practice of medicine. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 12 TC 8 Z9 8 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1759-8478 J9 J NEUROINTERV SURG JI J. NeuroInterventional Surg. PD NOV PY 2012 VL 4 IS 6 BP 468 EP 472 DI 10.1136/neurintsurg-2011-010141 PG 5 WC Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 029MX UT WOS:000310501000023 PM 21990546 ER PT J AU Heath, JA Oh, LJ Clarke, NE Wolfe, J AF Heath, John A. Oh, Luke J. Clarke, Naomi E. Wolfe, Joanne TI Complementary and Alternative Medicine Use in Children with Cancer at the End of Life SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID PEDIATRIC ONCOLOGY PATIENTS; PALLIATIVE CARE; THERAPIES; PREVALENCE; TURKEY AB Background: The use of complementary and alternative medicines (CAM) in patients with cancer is well recognized. Little is known, however, about the use of CAM in children with cancer during the end-of-life period. Methods: We interviewed 96 parents of children who had died of cancer in Melbourne, Australia between 1996 and 2004 to establish the prevalence of CAM use during the end-of-life period. Factors affecting the use of CAM were explored. We also determined the perceived efficacy of CAM use and its effect on the overall experience of end-of-life care. Results: Thirty percent of parents caring for a child with cancer reported using some form of CAM during the end-of-life period, with 44% of these families using more than one type. The most common therapies used were organic foods, faith healing, and homeopathy. There was a strong correlation between open discussion about treatment alternatives with the treating physician and parental use of CAM. The majority (78%) of respondents felt CAM use had benefited their child significantly and most felt it had not caused additional suffering. Conclusions: A significant number of children with cancer are administered CAM during the end-of-life period and most families in our study had found it beneficial. The main focus should continue to be on open and honest communication between caregivers and families in order to provide the best possible holistic care. C1 [Heath, John A.; Oh, Luke J.; Clarke, Naomi E.] Royal Childrens Hosp, Childrens Canc Ctr, Melbourne, Vic, Australia. [Heath, John A.; Oh, Luke J.; Clarke, Naomi E.] Univ Melbourne, Dept Pediat, Melbourne, Vic 3010, Australia. [Wolfe, Joanne] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolfe, Joanne] Harvard Univ, Dept Pediat, Cambridge, MA 02138 USA. RP Heath, JA (reprint author), Royal Childrens Hosp, Flemington Rd, Parkville, Vic 3052, Australia. EM john.heath@rch.org.au FU NHMRC Palliative Care Grant FX This study was supported by an NHMRC Palliative Care Grant. NR 31 TC 6 Z9 6 U1 0 U2 19 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 J9 J PALLIAT MED JI J. Palliat. Med. PD NOV PY 2012 VL 15 IS 11 BP 1218 EP 1221 DI 10.1089/jpm.2012.0150 PG 4 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 030VX UT WOS:000310599300011 PM 22908860 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI A "Shot Heard 'Round the World" on Cancer Drug Costs? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA USA. [Burstein, Harold J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2012 VL 10 IS 11 BP 1315 EP 1316 PG 2 WC Oncology SC Oncology GA 033TB UT WOS:000310822900001 PM 23138159 ER PT J AU Morgan, RJ Alvarez, RD Armstrong, DK Burger, RA Castells, M Chen, LM Copeland, L Crispens, MA Gershenson, D Gray, H Hakam, A Havrilesky, LJ Johnston, C Lele, S Martin, L Matulonis, UA O'Malley, DM Penson, RT Remmenga, SW Sabbatini, P Santoso, JT Schilder, RJ Schink, J Teng, N Werner, TL Hughes, M Dwyer, MA AF Morgan, Robert J., Jr. Alvarez, Ronald D. Armstrong, Deborah K. Burger, Robert A. Castells, Mariana Chen, Lee-may Copeland, Larry Crispens, Marta Ann Gershenson, David Gray, Heidi Hakam, Ardeshir Havrilesky, Laura J. Johnston, Carolyn Lele, Shashikant Martin, Lainie Matulonis, Ursula A. O'Malley, David M. Penson, Richard T. Remmenga, Steven W. Sabbatini, Paul Santoso, Joseph T. Schilder, Russell J. Schink, Julian Teng, Nelson Werner, Theresa L. Hughes, Miranda Dwyer, Mary A. TI Ovarian Cancer, Version 3.2012 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PEGYLATED LIPOSOMAL DOXORUBICIN; RECURRENT EPITHELIAL OVARIAN; PRIMARY DEBULKING SURGERY; ADVANCED-STAGE OVARIAN; PHASE-III TRIAL; NEOADJUVANT CHEMOTHERAPY; HYPERSENSITIVITY REACTIONS; FALLOPIAN-TUBE; CARBOPLATIN HYPERSENSITIVITY; DRUG HYPERSENSITIVITY AB These NCCN Guidelines Insights focus on the major updates for the 2012 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Ovarian Cancer by describing how and why the new recommendations were made. The 6 update topics were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials, and include: 1) screening, 2) diagnostic tests for assessing pelvic masses, 3) primary treatment using neoadjuvant chemotherapy, 4) primary adjuvant treatment using bevacizumab in combination with chemotherapy, 5) therapy for recurrent disease, and 6) management of drug/hypersensitivity reactions. These NCCN Guidelines Insights also discuss why some recommendations were not made (eg, panel members did not feel the new data warranted changing the guideline). See "Updates" in the NCCN Guidelines for Ovarian Cancer for a complete list of all the recent revisions. (JNCCN 2012;10:1339-1349) C1 [Morgan, Robert J., Jr.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Alvarez, Ronald D.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Armstrong, Deborah K.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Burger, Robert A.; Martin, Lainie; Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Matulonis, Ursula A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Chen, Lee-may] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Copeland, Larry; O'Malley, David M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Copeland, Larry; O'Malley, David M.] Solove Res Inst, Columbus, OH 43210 USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Gershenson, David] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Gray, Heidi] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Hakam, Ardeshir] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Havrilesky, Laura J.] Duke Canc Inst, Durham, NC USA. [Johnston, Carolyn] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lele, Shashikant] Roswell Pk Canc Inst, Buffalo, NY USA. [Penson, Richard T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Remmenga, Steven W.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Sabbatini, Paul] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Santoso, Joseph T.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Schink, Julian] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Teng, Nelson] Stanford Canc Inst, Stanford, CA USA. [Werner, Theresa L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Schink, Julian; Teng, Nelson] Natl Comprehens Canc Network, Washington, DC USA. RP Morgan, RJ (reprint author), City Hope Comprehens Canc Ctr, Duarte, CA USA. RI OMalley, David/E-3789-2011 NR 62 TC 37 Z9 38 U1 1 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2012 VL 10 IS 11 BP 1339 EP 1349 PG 11 WC Oncology SC Oncology GA 033TB UT WOS:000310822900005 PM 23138163 ER PT J AU Choudhury, AD Kantoff, PW AF Choudhury, Atish D. Kantoff, Philip W. TI New Agents in Metastatic Prostate Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PHASE-III TRIAL; INCREASED SURVIVAL; PLUS PREDNISONE; SIPULEUCEL-T; DOUBLE-BLIND; IMMUNOTHERAPY; THERAPY; KETOCONAZOLE; ANTIANDROGEN AB Discoveries of molecular mechanisms and therapeutic targets in metastatic castration-resistant prostate cancer (CRPC) have led to significant advancements in the development of effective agents in this setting, with diverse mechanisms of action. Within the past 2 years, 5 agents have been approved for the treatment of patients with metastatic CRPC (cabazitaxel, abiraterone, sipuleucel-T, denosumab, and enzalutamide), and another (Alpharadin) has shown overall survival benefit in a phase III trial. This article summarizes the phase III data showing clinical benefit from these agents, highlights other promising therapies in phase III studies as single agents (PROSTVAC-VF, ipilimumab, cabozantinib), discusses important unanswered questions regarding these therapies, and provides a schema for their use based on current regulatory approval and how this is likely to evolve as data from ongoing studies are reported. Although curative interventions in metastatic CRPC still do not exist, the hope is that optimization of therapeutic strategies can reduce the morbidity and mortality associated with this disease. (JNCCN 2012;10:1403-1409) C1 [Choudhury, Atish D.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choudhury, Atish D.] Broad Inst Harvard & MIT, Cambridge, MA USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mailstop Dana 1230, Boston, MA 02115 USA. EM philip_kantoff@dfci.harvard.edu FU NCI NIH HHS [T32 CA009172] NR 36 TC 8 Z9 8 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2012 VL 10 IS 11 BP 1403 EP 1409 PG 7 WC Oncology SC Oncology GA 033TB UT WOS:000310822900010 PM 23138168 ER PT J AU Baden, LR Bensinger, W Angarone, M Casper, C Dubberke, ER Freifeld, AG Garzon, R Greene, JN Greer, JP Ito, JI Karp, JE Kaul, DR King, E Mackler, E Marr, KA Montoya, JG Morris-Engemann, A Pappas, PG Rolston, K Segal, B Seo, SK Swaminathan, S Naganuma, M Shead, DA AF Baden, Lindsey Robert Bensinger, William Angarone, Michael Casper, Corey Dubberke, Erik R. Freifeld, Alison G. Garzon, Ramiro Greene, John N. Greer, John P. Ito, James I. Karp, Judith E. Kaul, Daniel R. King, Earl Mackler, Emily Marr, Kieren A. Montoya, Jose G. Morris-Engemann, Ashley Pappas, Peter G. Rolston, Ken Segal, Brahm Seo, Susan K. Swaminathan, Sankar Naganuma, Maoko Shead, Dorothy A. TI Prevention and Treatment of Cancer-Related Infections SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID STEM-CELL TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; HEPATITIS-B-VIRUS; PNEUMOCYSTIS-CARINII-PNEUMONIA; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; PLACEBO-CONTROLLED TRIAL; HERPES-SIMPLEX-VIRUS; VERSUS-HOST-DISEASE; INVASIVE PULMONARY ASPERGILLOSIS AB Patients with cancer are at increased risk for developing infectious complications during the course of their disease and treatment. The following sections of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections provide an overview of the risk factors for infectious complications, recommendations for infectious risk categorization, and strategies for prevention of infections in high-risk patient populations with cancer. Individualized risk evaluation for infections and incorporation of preventative measures are essential components of the overall spectrum of cancer care, and may contribute to optimizing treatment outcomes for patients. (JNCCN 2012;10:1412-1445) C1 [Baden, Lindsey Robert] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Bensinger, William; Casper, Corey] Fred Hutchinson Canc Res Ctr Seattle Canc Care Al, Seattle, WA USA. [Angarone, Michael] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Dubberke, Erik R.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Freifeld, Alison G.] Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Garzon, Ramiro] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Garzon, Ramiro] Solove Res Inst, Columbus, OH USA. [Greene, John N.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Greer, John P.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ito, James I.] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Karp, Judith E.; Marr, Kieren A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Kaul, Daniel R.; Mackler, Emily] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [King, Earl] Fox Chase Canc Ctr, Philadelphia, PA USA. [Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA. [Morris-Engemann, Ashley] Duke Comprehens Canc Ctr, Durham, NC USA. [Pappas, Peter G.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Rolston, Ken] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Segal, Brahm] Roswell Pk Canc Inst, Buffalo, NY USA. [Seo, Susan K.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Swaminathan, Sankar] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Baden, LR (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. NR 228 TC 50 Z9 52 U1 1 U2 9 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2012 VL 10 IS 11 BP 1412 EP 1445 PG 34 WC Oncology SC Oncology GA 033TB UT WOS:000310822900011 PM 23138169 ER PT J AU Issa, NC Baden, LR AF Issa, Nicolas C. Baden, Lindsey R. TI Current Issues in Vaccines for Adult Patients With Hematologic Malignancies SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID BONE-MARROW-TRANSPLANTATION; HEMATOPOIETIC-CELL TRANSPLANTATION; PNEUMOCOCCAL CONJUGATE VACCINE; PROTECTIVE ANTIBODY-RESPONSES; RESPIRATORY VIRUS-INFECTIONS; NON-HODGKINS-LYMPHOMA; INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; RUBELLA VACCINE; RECIPIENTS AB Vaccination is an important strategy for preventing infections in patients with hematologic malignancies. Hematopoietic cell transplant (HCT) recipients have diminished immunity against vaccinepreventable diseases after transplantation. Optimal timing for initiating immunization in the context of hematologic malignancies and after HCT, however, is not well defined, and data on the magnitude and duration of immune response to vaccines in this population are lacking. Factors such as degree of immunosuppression, administration of monoclonal antibodies, time after HCT, and presence or absence of chronic graft-versus-host disease may influence the immune response to vaccines and may pose safety concerns for certain vaccines, such as live-attenuated immunogens. Patients who received certain monoclonal antibodies (eg, rituximab, alemtuzumab) less than 6 months before vaccination have poorer immune responses to vaccines. New advancements in vaccine development are warranted to improve safety and immunogenicity of vaccination in immunocompromised patients. (JNCCN 2012;10:1447-1454) C1 [Issa, Nicolas C.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Issa, NC (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB A-4, Boston, MA 02115 USA. EM nissa@partners.org NR 49 TC 8 Z9 9 U1 0 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD NOV PY 2012 VL 10 IS 11 BP 1447 EP 1454 PG 8 WC Oncology SC Oncology GA 033TB UT WOS:000310822900012 PM 23138170 ER PT J AU Adams, SR Durfee, S Pettigrew, C Katz, D Jennings, R Ecker, J House, M Benson, CB Wolfberg, A AF Adams, Sonia R. Durfee, Sara Pettigrew, Courtenay Katz, Daniel Jennings, Russell Ecker, Jeffrey House, Michael Benson, Carol B. Wolfberg, Adam TI Accuracy of Sonography to Predict Estimated Weight in Fetuses With Gastroschisis SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE estimation; fetal weight; gastroschisis; sonography ID ABDOMINAL-WALL DEFECTS; FETAL WEIGHT; GROWTH-RETARDATION; SURVEILLANCE; DIAGNOSIS; HEAD AB Objectives-The purpose of this study was to determine whether sonographic formulas for estimating fetal weight are as accurate for fetuses affected with gastroschisis as they are for healthy fetuses. We hypothesized that because the most commonly used Hadlock formulas rely on the abdominal circumference as a biometric variable, estimates of birth weight are less reliable in fetuses with gastroschisis than in healthy fetuses. Methods-We performed a chart review of all fetuses with a prenatal diagnosis of gastroschisis at 3 tertiary care institutions from 1990 to 2008. Charts were reviewed for clinical and sonographic data. The estimated fetal weight at the prenatal sonogram closest to delivery was compared to the birth weight. Published Hadlock formulas using 4 biometric parameters were used to calculate the estimated fetal weight. Data analysis was performed using the Student t test and chi(2) test for continuous and categorical variables, respectively. Results-One hundred eleven patients with gastroschisis were identified. Sixty-six patients had a prenatal sonogram with a calculated estimated fetal weight within 7 days of delivery; 88 patients had a sonogram within 14 days. The mean birth weights +/- SD were 2292 +/- 559 and 2477 +/- 531 g in the 0- to 7- and 8- to 14-day groups, respectively. Sonographic biometric measurements underestimated the birth weight by an average of 5.6%. Intrauterine growth restriction was predicted in 72% of all pregnancies but was only present in 52%. Conclusions-Our study shows a systematic error of birth weight underestimation when using the Hadlock formulas in fetuses affected with gastroschisis. C1 [Adams, Sonia R.] Tufts Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02111 USA. [Durfee, Sara; Benson, Carol B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Durfee, Sara; Katz, Daniel; Ecker, Jeffrey; Benson, Carol B.; Wolfberg, Adam] Harvard Univ, Cambridge, MA 02138 USA. [Katz, Daniel; Ecker, Jeffrey] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Jennings, Russell; Wolfberg, Adam] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Adams, SR (reprint author), Tufts Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, 800 Washington St, Boston, MA 02111 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2012 VL 31 IS 11 BP 1753 EP 1758 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 031OY UT WOS:000310653000007 PM 23091245 ER PT J AU Ross, RW Galsky, MD Scher, HI Magidson, J Wassmann, K Lee, GSM Katz, L Subudhi, SK Anand, A Fleisher, M Kantoff, PW Oh, WK AF Ross, Robert W. Galsky, Matthew D. Scher, Howard I. Magidson, Jay Wassmann, Karl Lee, Gwo-Shu Mary Katz, Leah Subudhi, Sumit K. Anand, Aseem Fleisher, Martin Kantoff, Philip W. Oh, William K. TI A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study SO LANCET ONCOLOGY LA English DT Article ID TISSUE INHIBITOR; SURVIVAL; CELLS; GENE; MICROARRAY; TIME; MACROPHAGES; PROGRESSION; DISEASE; POINTS AB Background Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer. Methods Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival. Findings A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34.9 months (median survival was not reached) and a high-risk group with a median survival of 7.8 months (95% CI 1.8-13.9; p<0.0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0.90 [95% CI 0.78-0.96] vs 0.65 [0.52-0.78]; p=0.0067). Interpretation Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study. Funding Source MDX. C1 [Ross, Robert W.; Lee, Gwo-Shu Mary; Katz, Leah; Kantoff, Philip W.] Dana Farber Canc Inst, Div Solid Tumor Oncol, Dept Med, Boston, MA 02115 USA. [Ross, Robert W.; Lee, Gwo-Shu Mary; Katz, Leah; Kantoff, Philip W.] Harvard Univ, Sch Med, Boston, MA USA. [Galsky, Matthew D.; Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, Dept Med, Div Hematol Oncol, New York, NY 10029 USA. [Scher, Howard I.; Subudhi, Sumit K.; Anand, Aseem] Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. [Scher, Howard I.; Subudhi, Sumit K.; Anand, Aseem] Weill Cornell Med Coll, New York, NY USA. [Magidson, Jay] Stat Innovat, Belmont, MA USA. [Wassmann, Karl] GeneNews, Boston, MA USA. [Fleisher, Martin] Mem Sloan Kettering Canc Ctr, Dept Clin Labs, New York, NY 10021 USA. RP Oh, WK (reprint author), Mt Sinai Sch Med, Tisch Canc Inst, Div Hematol & Med Oncol, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. EM william.oh@mssm.edu RI Oh, William/B-9163-2012; Anand, Aseem/P-1214-2014 OI Oh, William/0000-0001-5113-8147; Anand, Aseem/0000-0002-3606-540X FU Source MDx FX This study was funded by Source MDx. Source MDx is no longer in business. NR 39 TC 40 Z9 40 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2012 VL 13 IS 11 BP 1105 EP 1113 DI 10.1016/S1470-2045(12)70263-2 PG 9 WC Oncology SC Oncology GA 030KZ UT WOS:000310570900041 PM 23059047 ER PT J AU Kourkoumpetis, TK Desalermos, A Muhammed, M Mylonakis, E AF Kourkoumpetis, Themistoklis K. Desalermos, Athanasios Muhammed, Maged Mylonakis, Eleftherios TI Central Nervous System Aspergillosis A Series of 14 Cases From a General Hospital and Review of 123 Cases From the Literature SO MEDICINE LA English DT Review ID OF-THE-LITERATURE; MUCOCUTANEOUS FUNGAL-INFECTIONS; INVASIVE ASPERGILLOSIS; CEREBRAL ASPERGILLOSIS; IMMUNOCOMPETENT PATIENT; AMPHOTERICIN-B; BRAIN-ABSCESS; CEREBROSPINAL-FLUID; INTRACRANIAL ASPERGILLOSIS; IMMUNOCOMPROMISED PATIENTS AB Central nervous system (CNS) aspergillosis is a highly fatal infection. We review the clinical presentation, diagnosis, and outcome of this infection and present a case series of 14 consecutive patients with CNS aspergillosis admitted to Massachusetts General Hospital (MGH) from 2000 to 2011. We also review 123 cases reported in the literature during that time. We included only proven CNS aspergillosis cases conforming to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal infections. In the MGH case series, neutropenia, hematologic malignancies, autoimmune diseases requiring steroid treatment, and solid organ transplantation were the predominant comorbid conditions. Notably, all MGH patients were immunosuppressed, and more than half (n = 8) had a history of previous brain injury, unrelated to their index hospitalization. For most MGH patients (11 of 14), the lung was the primary focus of aspergillosis, while 2 had paranasal sinus involvement, and 1 had primary Aspergillus discitis. Among reported cases, paranasal sinuses (27.6%) and the lung (26.8%) were the primary foci of infection, whereas 22% of those cases had no obvious primary organ involvement. Although a selection bias should be considered, especially among published cases, our findings suggest that patients who underwent neurosurgery had improved survival, with MGH and literature patients having 25% and 28.6% mortality, respectively, compared to 100% and 60.4%, respectively, among patients who received only medical treatment. Although this was not the case among MGH patients, CNS aspergillosis can affect patients without significant immune suppression, as indicated by the high number of reported immunocompetent cases. In conclusion, mortality among CNS aspergillosis patients remains high, and the infection may be more common among patients with previous brain pathology. When indicated, neurosurgical procedures may improve prognosis. C1 [Kourkoumpetis, Themistoklis K.; Desalermos, Athanasios; Muhammed, Maged; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis,Dept Med, Boston, MA USA. RP Mylonakis, E (reprint author), Brown Univ, Warren Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA. EM emylonakis@lifespan.org FU Astellas Pharma, Inc. FX The Mylonakis laboratory has received research funding from Astellas Pharma, Inc. The funds were for research unrelated to the current work. For the remaining authors no conflicts of interest were declared. NR 102 TC 23 Z9 24 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2012 VL 91 IS 6 BP 328 EP 336 DI 10.1097/MD.0b013e318274cd77 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 033IK UT WOS:000310787400004 PM 23117848 ER PT J AU Cauley, JA Danielson, ME Greendale, GA Finkelstein, JS Chang, YF Lo, JC Crandall, CJ Neer, RM Ruppert, K Meyn, L Prairie, BA Sowers, MR AF Cauley, Jane A. Danielson, Michelle E. Greendale, Gail A. Finkelstein, Joel S. Chang, Yue-Fang Lo, Joan C. Crandall, Carolyn J. Neer, Robert M. Ruppert, Kristine Meyn, Leslie Prairie, Beth A. Sowers, MaryFran R. TI Bone resorption and fracture across the menopausal transition: the Study of Women's Health Across the Nation SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE Bone resorption; Fracture; Menopause; Osteoporosis; Bone mineral density ID BIOCHEMICAL MARKERS; OSTEOPOROTIC FRACTURES; ENDOGENOUS HORMONES; MINERAL DENSITY; ELDERLY-WOMEN; HIP FRACTURE; OLDER WOMEN; PERIMENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; VERTEBRAL FRACTURES AB Objective: Bone turnover markers (BTMs) predict fracture in older women, whereas data on younger women are lacking. To test the hypothesis that BTMs measured before and after menopause predict fracture risk, we performed a cohort study of 2,305 women. Methods: Women attended up to nine clinic visits for an average of 7.6 +/- 1.6 years; all were aged 42 to 52 years and were premenopausal or early perimenopausal at baseline. Incident fractures were self-reported. Serum osteocalcin and urinary cross-linked N-telopeptide of type I collagen (NTX) were measured at baseline. NTX was measured at each annual follow-up. Interval-censored survival models or generalized estimating equations were used to test whether baseline BTMs and changes in NTX, respectively, were associated with fracture risk. Hazard ratios (HRs) or odds ratios were calculated with 95% CIs. Results: Women who experienced fractures (n = 184) had about a 10% higher baseline median NTX (34.4 vs 31.5 nanomoles of bone collagen equivalents per liter per nanomole of creatinine per liter; P = 0.001), but there was no difference in osteocalcin. A 1-SD decrease in lumbar spine bone mineral density (BMD) measured pre-menopausally was associated with a higher fracture risk during menopause (HR, 1.50; 95% CI, 1.28-1.68). Women with a baseline NTX greater than the median had a 45% higher risk of fracture, multivariable-adjusted (HR, 1.46; 95% CI, 1.05-2.26). The HR of fracture among women with both the lowest spine BMD (quartile 1) and the highest NTX (quartile 4) at baseline was 2.87 (95% CI, 1.61-6.01), compared with women with lower NTX and higher BMD. Women whose NTX increased more than the median had a higher risk of fracture (odds ratio, 1.51; 95% CI, 1.08-2.10). Women who had baseline NTX greater than the median experienced greater loss of spine and hip BMD. Conclusions: A higher urinary NTX excretion measured before menopause and across menopause is associated with a higher risk of fracture. Our results are consistent with the pathophysiology of transmenopausal changes in bone strength. C1 [Cauley, Jane A.; Danielson, Michelle E.; Chang, Yue-Fang; Ruppert, Kristine; Meyn, Leslie] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Greendale, Gail A.; Crandall, Carolyn J.] Univ Calif Los Angeles, Los Angeles, CA USA. [Finkelstein, Joel S.; Neer, Robert M.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Lo, Joan C.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Prairie, Beth A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Sowers, MaryFran R.] Univ Michigan, Ann Arbor, MI 48109 USA. RP Cauley, JA (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 DeSoto St,Crabtree A510, Pittsburgh, PA 15261 USA. EM jcauley@edc.pitt.edu RI Ruppert, Kristine/C-2555-2016; OI Ruppert, Kristine/0000-0002-3008-6584; Cauley, Jane A/0000-0003-0752-4408 FU National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging; National Institute of Nursing Research; NIH Office of Research on Women's Health [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; Swiss Precision Diagnostics Development Company Limited Priory (Business Park Bedford, UK); Department of Defense [DAMD17-96-6118]; NIH [K24-DK02759, RR-1066]; Iris Cantor-University of California, Los Angeles Women's Health Center; University of California, Los Angeles Center of Excellence in Women's Health [RFP 282-97-0025]; Novartis Pharmaceuticals; Merck FX The Study of Women's Health Across the Nation received grant support from the National Institutes of Health (NIH), Department of Health and Human Services, through the National Institute on Aging, the National Institute of Nursing Research, and the NIH Office of Research on Women's Health (grants NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, and AG012495). Measures of cross-linked N-telopeptide of type I collagen were funded by the Swiss Precision Diagnostics Development Company Limited Priory (Business Park Bedford, UK) under the direction of Dr. Sarah Johnson. This work was also supported by Department of Defense grant DAMD17-96-6118; NIH grant K24-DK02759 (to J.S.F.); the Iris Cantor-University of California, Los Angeles Women's Health Center; University of California, Los Angeles Center of Excellence in Women's Health grant RFP 282-97-0025 (to G. A. G.); and NIH grant RR-1066 (to Massachusetts General Hospital, Boston, MA).; Dr. Cauley has received research support and consulting fees from Novartis Pharmaceuticals and Merck. Drs. Chang, Crandall, Danielson, Lo, Finkelstein, Greendale, Neer, Prairie, and Ruppert, as well as Ms. Meyn, have no conflicts of interest to report. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging, the National Institute of Nursing Research, the Office of Research on Women's Health, or the NIH. NR 44 TC 14 Z9 15 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV PY 2012 VL 19 IS 11 BP 1200 EP 1207 DI 10.1097/gme.0b013e31825ae17e PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 030OA UT WOS:000310578800008 PM 22850443 ER PT J AU Desimmie, BA Humbert, M Lescrinier, E Hendrix, J Vets, S Gijsbers, R Ruprecht, RM Dietrich, U Debyser, Z Christ, F AF Desimmie, Belete A. Humbert, Michael Lescrinier, Eveline Hendrix, Jelle Vets, Sofie Gijsbers, Rik Ruprecht, Ruth M. Dietrich, Ursula Debyser, Zeger Christ, Frauke TI Phage Display-directed Discovery of LEDGF/p75 Binding Cyclic Peptide Inhibitors of HIV Replication SO MOLECULAR THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS REPLICATION; IN-VITRO; BLOCKING INTERACTIONS; INTEGRASE; PROTEINS; TARGET; RECEPTOR; POTENT; DOMAIN; TRANSCRIPTION AB The interaction between the human immunodeficiency virus (HIV) integrase (IN) and its cellular cofactor lens epithelium-derived growth factor (LEDGF/p75) is crucial for HIV replication. While recently discovered LEDGINs inhibit HIV-1 replication by occupying the LEDGF/p75 pocket in IN, it remained to be demonstrated whether LEDGF/p75 by itself can be targeted. By phage display we identified cyclic peptides (CPs) as the first LEDGF/p75 ligands that inhibit the LEDGF/p75 IN interaction. The CPs inhibit HIV replication in different cell lines without overt toxicity. In accord with the role of LEDGF/p75 in HIV integration and its inhibition by LEDGINs, CP64, and CP65 block HIV replication primarily by inhibiting the integration step. The CPs retained activity against HIV strains resistant to raltegravir or LEDGINs. Saturation transfer difference (STD) NMR showed residues in CP64 that strongly interact with LEDGF/p75 but not with HIV IN. Mutational analysis identified tryptophan as an important residue responsible for the activity of the peptides. Serial passaging of virus in the presence of CPs did not yield resistant strains. Our work provides proof-of-concept for direct targeting of LEDGF/p75 as novel therapeutic strategy and the CPs thereby serve as scaffold for future development of new HIV therapeutics. Received 2 March 2012; accepted 23 April 2012; advance online publication 24 July 2012. doi:10.1038/mt.2012.132 C1 [Desimmie, Belete A.; Vets, Sofie; Gijsbers, Rik; Debyser, Zeger; Christ, Frauke] Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Mol Virol & Gene Therapy, B-3000 Louvain, Flanders, Belgium. [Desimmie, Belete A.; Vets, Sofie; Gijsbers, Rik; Debyser, Zeger; Christ, Frauke] IRC Kulak, B-3000 Louvain, Flanders, Belgium. [Humbert, Michael; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Humbert, Michael; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Lescrinier, Eveline] Katholieke Univ Leuven, BioMacS, Rega Inst Med Res, Med Chem Lab, B-3000 Louvain, Flanders, Belgium. [Hendrix, Jelle] Katholieke Univ Leuven, Div Mol & Nanomat, Res Grp Photochem & Spect, B-3000 Louvain, Flanders, Belgium. [Dietrich, Ursula] Inst Biomed Res, D-60596 Frankfurt, Germany. RP Christ, F (reprint author), Katholieke Univ Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Mol Virol & Gene Therapy, Kapucijnenvoer 33, B-3000 Louvain, Flanders, Belgium. EM ursula.dietrich@em.uni-frankfurt.de; zeger.debyser@med.kuleuven.be; frauke.christ@med.kuleuven.be RI Hendrix, Jelle/A-8182-2013; OI debyser, zeger/0000-0002-3982-1565 FU European Commission through the European Consortia TRIoH [LSHB-CT-2003-503480]; European Commission through the European Consortia THINC [HEALTH-F3-2008-201032]; Flemish FWO; KU Leuven BOF; NIH [P01 AI048240] FX We thank Barbara Van Remoortel, Nam Joo Van Der Veken, Martine Michiels, and Linda Desender for excellent technical assistance. We thank Dr R. Clayton (Tibotec) for providing us with raltegravir. We thank Dr Yves Engelborghs (KU Leuven) for access to the Zeiss LSM 510 system. Research was funded by the European Commission (FP6/FP7) through the European Consortia TRIoH (LSHB-CT-2003-503480) and THINC (HEALTH-F3-2008-201032) and additionally by the Flemish FWO and KU Leuven BOF. F.C. is an OF fellow and B.A.D. is a DBOF fellow of the KU Leuven. M.H. and R.M.R. were supported by NIH grant P01 AI048240. The authors declared no conflict of interest. NR 49 TC 27 Z9 27 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD NOV PY 2012 VL 20 IS 11 BP 2064 EP 2075 DI 10.1038/mt.2012.132 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 033AL UT WOS:000310764500010 PM 22828501 ER PT J AU Klatt, NR Estes, JD Sun, X Ortiz, AM Barber, JS Harris, LD Cervasi, B Yokomizo, LK Pan, L Vinton, CL Tabb, B Canary, LA Dang, Q Hirsch, VM Alter, G Belkaid, Y Lifson, JD Silvestri, G Milner, JD Paiardini, M Haddad, EK Brenchley, JM AF Klatt, N. R. Estes, J. D. Sun, X. Ortiz, A. M. Barber, J. S. Harris, L. D. Cervasi, B. Yokomizo, L. K. Pan, L. Vinton, C. L. Tabb, B. Canary, L. A. Dang, Q. Hirsch, V. M. Alter, G. Belkaid, Y. Lifson, J. D. Silvestri, G. Milner, J. D. Paiardini, M. Haddad, E. K. Brenchley, J. M. TI Loss of mucosal CD103+ DCs and IL-17+ and IL-22+ lymphocytes is associated with mucosal damage in SIV infection SO MUCOSAL IMMUNOLOGY LA English DT Article ID INNATE LYMPHOID-CELLS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; RETINOIC-ACID; MICROBIAL TRANSLOCATION; HIV-INFECTION; IMMUNE ACTIVATION; TH17 CELLS; GENE-EXPRESSION; DENDRITIC CELLS AB Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV) disease progression is associated with multifocal damage to the gastrointestinal tract epithelial barrier that correlates with microbial translocation and persistent pathological immune activation, but the underlying mechanisms remain unclear. Investigating alterations in mucosal immunity during SIV infection, we found that damage to the colonic epithelial barrier was associated with loss of multiple lineages of interleukin (IL)-17-producing lymphocytes, cells that microarray analysis showed expressed genes important for enterocyte homeostasis, including IL-22. IL-22-producing lymphocytes were also lost after SIV infection. Potentially explaining coordinate loss of these distinct populations, we also observed loss of CD103+ dendritic cells (DCs) after SIV infection, which associated with the loss of IL-17- and IL-22-producing lymphocytes. CD103+ DCs expressed genes associated with promotion of IL-17/IL-22+ cells, and coculture of CD103+ DCs and naive T cells led to increased IL17A and RORc expression in differentiating T cells. These results reveal complex interactions between mucosal immune cell subsets providing potential mechanistic insights into mechanisms of mucosal immune dysregulation during HIV/SIV infection, and offer hints for development of novel therapeutic strategies to address this aspect of AIDS virus pathogenesis. C1 [Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. [Klatt, N. R.; Harris, L. D.; Vinton, C. L.; Canary, L. A.; Dang, Q.; Hirsch, V. M.; Belkaid, Y.; Brenchley, J. M.] NIAID, Program Barrier Immun & Repair, NIH, Bethesda, MD 20892 USA. [Estes, J. D.; Tabb, B.; Lifson, J. D.] Frederick Natl Lab Canc Res, SAIC Frederick, AIDS & Canc Virus Program, Frederick, MD USA. [Sun, X.; Pan, L.; Haddad, E. K.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Ortiz, A. M.; Cervasi, B.; Silvestri, G.; Paiardini, M.] Emory Univ, Yerkes Natl Primate Res Ctr, Pathol & Lab Med, Atlanta, GA 30322 USA. [Ortiz, A. M.] Univ Penn, Sch Med, Cellular & Mol Biol Program, Philadelphia, PA 19104 USA. [Barber, J. S.; Yokomizo, L. K.; Milner, J. D.] NIAD, Lab Allerg Dis, NIH, Bethesda, MD USA. [Alter, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ragon Inst, Boston, MA USA. [Belkaid, Y.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Brenchley, JM (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbrenchl@mail.nih.gov FU Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institutes of Health [R01 AI-084836] FX We would like to acknowledge Heather Cronise, JoAnne Swerczek, Richard Herbert, and all the veterinary staff at the NIH animal center. We would like to thank Tracy Meeker and Stephanie Ehnert, and the veterinary staff at YNPRC. We would like to thank the Cleveland Immunopathogenesis Consortium (BBC/CLIC) for advice and helpful discussions. We would like to thank Mark Cameron and Peter Wilkinson from the Genomics core at VGTI-FL for gene array consultation. Histology support was provided by the Pathology/Histotechnology Laboratory (PHL) core service located at the National Cancer Institute-Frederick, Frederick, MD, USA. These studies were supported by the Intramural National Institute of Allergy and Infectious Diseases, US National Institutes of Health program, and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E, and National Institutes of Health R01 AI-084836 under M Paiardini. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the United States. NR 57 TC 75 Z9 75 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1933-0219 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD NOV PY 2012 VL 5 IS 6 BP 646 EP 657 DI 10.1038/mi.2012.38 PG 12 WC Immunology SC Immunology GA 030LS UT WOS:000310572800007 PM 22643849 ER PT J AU Chen, HZ Ouseph, MM Li, J Pecot, T Chokshi, V Kent, L Bae, S Byrne, M Duran, C Comstock, G Trikha, P Mair, M Senapati, S Martin, CK Gandhi, S Wilson, N Liu, B Huang, YW Thompson, JC Raman, S Singh, S Leone, M Machiraju, R Huang, K Mo, XK Fernandez, S Kalaszczynska, I Wolgemuth, DJ Sicinski, P Huang, T Jin, V Leone, G AF Chen, Hui-Zi Ouseph, Madhu M. Li, Jing Pecot, Thierry Chokshi, Veda Kent, Lindsey Bae, Sooin Byrne, Morgan Duran, Camille Comstock, Grant Trikha, Prashant Mair, Markus Senapati, Shantibhusan Martin, Chelsea K. Gandhi, Sagar Wilson, Nicholas Liu, Bin Huang, Yi-Wen Thompson, John C. Raman, Sundaresan Singh, Shantanu Leone, Marcelo Machiraju, Raghu Huang, Kun Mo, Xiaokui Fernandez, Soledad Kalaszczynska, Ilona Wolgemuth, Debra J. Sicinski, Piotr Huang, Tim Jin, Victor Leone, Gustavo TI Canonical and atypical E2Fs regulate the mammalian endocycle SO NATURE CELL BIOLOGY LA English DT Article ID TROPHOBLAST CELL-DIFFERENTIATION; MOUSE DEVELOPMENT; CYCLE CONTROL; S-PHASE; MICE; DNA; PROLIFERATION; LIVER; ENDOREPLICATION; TRANSCRIPTION AB The endocycle is a variant cell cycle consisting of successive DNA synthesis and gap phases that yield highly polyploid cells. Although essential formetazoan development, relatively little is known about its control or physiologic role in mammals. Using lineage-specific cre mice we identified two opposing arms of the E2F program, one driven by canonical transcription activation (E2F1, E2F2 and E2F3) and the other by atypical repression (E2F7 and E2F8), that converge on the regulation of endocycles in vivo. Ablation of canonical activators in the two endocycling tissues of mammals, trophoblast giant cells in the placenta and hepatocytes in the liver, augmented genome ploidy, whereas ablation of atypical repressors diminished ploidy. These two antagonistic arms coordinate the expression of a unique G2/M transcriptional program that is critical for mitosis, karyokinesis and cytokinesis. These results provide in vivo evidence for a direct role of E2F family members in regulating non-traditional cell cycles in mammals. C1 [Chen, Hui-Zi; Ouseph, Madhu M.; Li, Jing; Pecot, Thierry; Chokshi, Veda; Kent, Lindsey; Bae, Sooin; Byrne, Morgan; Duran, Camille; Comstock, Grant; Trikha, Prashant; Mair, Markus; Senapati, Shantibhusan; Martin, Chelsea K.; Gandhi, Sagar; Wilson, Nicholas; Liu, Bin; Thompson, John C.; Huang, Tim; Leone, Gustavo] Ohio State Univ, Dept Mol Genet, Dept Mol Virol Immunol & Med Genet, Solid Tumor Biol Program,Comprehens Canc Ctr, Columbus, OH 43210 USA. [Chen, Hui-Zi; Leone, Gustavo] Ohio State Univ, Coll Med, Med Scientist Training Program, Columbus, OH 43210 USA. [Chen, Hui-Zi; Leone, Gustavo] Ohio State Univ, Coll Med, Integrated Biomed Grad Program, Columbus, OH 43210 USA. [Ouseph, Madhu M.] Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA. [Huang, Yi-Wen] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA. [Mo, Xiaokui; Fernandez, Soledad] Ohio State Univ, Ctr Biostat, Off Hlth Sci, Columbus, OH 43210 USA. [Kalaszczynska, Ilona; Sicinski, Piotr] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Kalaszczynska, Ilona; Sicinski, Piotr] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02215 USA. [Wolgemuth, Debra J.] Columbia Univ, Med Ctr, Dept Genet & Dev, Dept Obstet & Gynecol,Inst Human Nutr, New York, NY 10032 USA. [Wolgemuth, Debra J.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. RP Leone, G (reprint author), Ohio State Univ, Dept Mol Genet, Dept Mol Virol Immunol & Med Genet, Solid Tumor Biol Program,Comprehens Canc Ctr, 484 W 12Th Ave, Columbus, OH 43210 USA. EM Gustavo.Leone@osumc.edu RI Machiraju, Raghu/D-5963-2012; Huang, Kun/E-3272-2011; OI Kalaszczynska, Ilona/0000-0001-6698-1372 FU NIH [R01CA85619, R01CA82259, R01HD047470, P01CA097189, R01CA132740]; Pew Charitable Trust Scholar Award; Leukemia & Lymphoma Society Scholar Award; Pelotonia Fellowship Award FX We thank L. Rawahneh, J. Moffitt and N. Lovett for excellent technical assistance with histology, and P. Wenzel for generating and collecting 123tko placentae. We also thank these individuals from OSUCCC Shared Resources: T. Wise, J. Palatini, H. Alders, P. Yan, P. Fada and B. Rodriguez (Microarray and Nucleic Acid Shared Resources); B. McElwain (Analytic Cytometry); R. Burry, K. Wolken, and B. Kemmenoe (Microscopy and Imaging); and K. La Perle (Comparative Pathology and Mouse Phenotyping). We are grateful for PL-1 antibodies provided by F. Talamantes (University of California, Santa Cruz, CA), Rcho-1 trophoblast stem cells from M. J. Soares (University of Kansas Medical Center, Kansas City, KS) and HepG2 cells from S. Jacobs. This work was funded by NIH grants to G.L. (R01CA85619, R01CA82259, R01HD047470, P01CA097189) and P.S. (R01CA132740). G.L. is a recipient of The Pew Charitable Trust Scholar Award and the Leukemia & Lymphoma Society Scholar Award. H-Z.C., M.M., S.S., S.R. and T. P. are recipients of the Pelotonia Fellowship Award. NR 59 TC 47 Z9 51 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2012 VL 14 IS 11 BP 1192 EP + DI 10.1038/ncb2595 PG 22 WC Cell Biology SC Cell Biology GA 033EX UT WOS:000310778100012 PM 23064266 ER PT J AU Yan, N Lieberman, J AF Yan, Nan Lieberman, Judy TI SAMHD1 does it again, now in resting T cells SO NATURE MEDICINE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; INNATE IMMUNE-RESPONSE; DENDRITIC CELLS; VPX; MACROPHAGES; PROTEIN AB A long-standing question in the HIV field is why HIV-1 fails to replicate in resting CD4(+) T cells. A new study shows that host deoxynucleoside triphosphate triphosphohydrolase (dNTPase) sterile a motif and histidine/aspartic domain-containing protein 1 (SAMHD1), previously shown to block HIV infection in myeloid cells, also restricts HIV replication in resting CD4(+) T cells by hydrolyzing dNTPs, which are needed for reverse transcription of the virus (pages 1682-1687). C1 [Yan, Nan] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. [Yan, Nan] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Lieberman, Judy] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Yan, N (reprint author), Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA. EM nan.yan@utsouthwestern.edu; lieberman@idi.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R01 AI102816] NR 14 TC 4 Z9 5 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2012 VL 18 IS 11 BP 1611 EP 1612 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 033YJ UT WOS:000310837000013 PM 23135508 ER PT J AU Sundaresan, NR Vasudevan, P Zhong, L Kim, G Samant, S Parekh, V Pillai, VB Ravindra, PV Gupta, M Jeevanandam, V Cunningham, JM Deng, CX Lombard, DB Mostoslavsky, R Gupta, MP AF Sundaresan, Nagalingam R. Vasudevan, Prabhakaran Zhong, Lei Kim, Gene Samant, Sadhana Parekh, Vishwas Pillai, Vinodkumar B. Ravindra, P. V. Gupta, Madhu Jeevanandam, Valluvan Cunningham, John M. Deng, Chu-Xia Lombard, David B. Mostoslavsky, Raul Gupta, Mahesh P. TI The sirtuin SIRT6 blocks IGF-Akt signaling and development of cardiac hypertrophy by targeting c-Jun SO NATURE MEDICINE LA English DT Article ID HEAVY-CHAIN EXPRESSION; FOCAL ADHESION KINASE; REGULATES LIFE-SPAN; CALORIE RESTRICTION; HISTONE DEACETYLASE; GENE-EXPRESSION; HEART-FAILURE; MICE; ACTIVATION; DISEASE AB Abnormal activation of insulin-like growth factor (IGF)-Akt signaling is implicated in the development of various diseases, including heart failure. However, the molecular mechanisms that regulate activation of this signaling pathway are not completely understood. Here we show that sirtuin 6 (SIRT6), a nuclear histone deacetylase, functions at the level of chromatin to directly attenuate IGF-Akt signaling. SIRT6-deficient mice developed cardiac hypertrophy and heart failure, whereas SIRT6 transgenic mice were protected from hypertrophic stimuli, indicating that SIRT6 acts as a negative regulator of cardiac hypertrophy. SIRT6-deficient mouse hearts showed hyperactivation of IGF signaling-related genes and their downstream targets. Mechanistically, SIRT6 binds to and suppresses the promoter of IGF signaling-related genes by interacting with c-Jun and deacetylating histone 3 at Lys9 (H3K9). We also found reduced SIRT6 expression in human failing hearts. These findings disclose a new link between SIRT6 and IGF-Akt signaling and implicate SIRT6 in the development of cardiac hypertrophy and failure. C1 [Sundaresan, Nagalingam R.; Samant, Sadhana; Pillai, Vinodkumar B.; Ravindra, P. V.; Jeevanandam, Valluvan; Gupta, Mahesh P.] Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, Chicago, IL 60637 USA. [Vasudevan, Prabhakaran; Parekh, Vishwas; Cunningham, John M.] Univ Chicago, Dept Pediat, Comm Dev Biol, Chicago, IL 60637 USA. [Zhong, Lei; Mostoslavsky, Raul] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Kim, Gene] Univ Chicago, Cardiol Sect, Dept Med, Chicago, IL 60637 USA. [Gupta, Madhu] Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60680 USA. [Deng, Chu-Xia] NIDDKD, US NIH, Bethesda, MD 20892 USA. [Lombard, David B.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Lombard, David B.] Univ Michigan, Inst Gerontol, Ann Arbor, MI 48109 USA. RP Gupta, MP (reprint author), Univ Chicago, Dept Surg, Comm Cellular & Mol Physiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM mgupta@surgery.bsd.uchicago.edu RI Parekh, Vishwas/B-7162-2014; deng, chuxia/N-6713-2016; OI Parekh, Vishwas/0000-0003-3131-2958; Ravindra, P V/0000-0003-4228-1843 FU US National Institutes of Health [RO1 HL-117041, HL-83423, 111455]; American Heart Association FX We thank F. Alt, Harvard Medical School, for providing SIRT6 knockout mice, E. Verdin, University of California, San Francisco, for providing Flag-SIRT6 wild-type and mutant plasmids, F. VanGool, Institut de Biologie, Universite Libre de Bruxelles, Gosselies, Belgium, for providing mouse-SIRT6 expression plasmid and K. Chua, Stanford University, for providing SIRT6 retroviral vectors and SIRT6 knockout MEFs. The alpha-MHC promoter vector used to make cardiac-specific SIRT6 transgenic mice was provided by J. Robbins, University of Cincinnati. This study was supported by US National Institutes of Health grants RO1 HL-117041, HL-83423 and 111455 to M. P. G. N.R.S. was supported by a postdoctoral fellowship from the American Heart Association. NR 46 TC 119 Z9 124 U1 3 U2 38 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2012 VL 18 IS 11 BP 1643 EP + DI 10.1038/nm.2961 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 033YJ UT WOS:000310837000024 PM 23086477 ER PT J AU Gather, MC AF Gather, Malte C. TI A rocky road to plasmonic lasers SO NATURE PHOTONICS LA English DT Letter ID NANOLASER; GAIN C1 [Gather, Malte C.] Tech Univ Dresden, Inst Angew Photophys, D-01062 Dresden, Germany. [Gather, Malte C.] Harvard Univ, Sch Med, Wellman Ctr, Boston, MA 02114 USA. [Gather, Malte C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gather, MC (reprint author), Tech Univ Dresden, Inst Angew Photophys, D-01062 Dresden, Germany. EM malte.gather@tu-dresden.de OI Gather, Malte/0000-0002-4857-5562 NR 11 TC 12 Z9 12 U1 3 U2 61 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1749-4885 J9 NAT PHOTONICS JI Nat. Photonics PD NOV PY 2012 VL 6 IS 11 BP 708 EP 708 DI 10.1038/nphoton.2012.281 PG 1 WC Optics; Physics, Applied SC Optics; Physics GA 034CS UT WOS:000310848300002 ER PT J AU Agus, DB Michor, F AF Agus, David B. Michor, Franziska TI The sciences converge to fight cancer SO NATURE PHYSICS LA English DT Editorial Material ID METASTATIC NICHE; RESISTANCE C1 [Agus, David B.] Univ So Calif, Keck Sch Med, Ctr Appl Mol Med, Beverly Hills, CA 90211 USA. [Agus, David B.] Univ So Calif, Viterbi Sch Engn, Ctr Appl Mol Med, Beverly Hills, CA 90211 USA. [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Agus, DB (reprint author), Univ So Calif, Keck Sch Med, Ctr Appl Mol Med, 9033 Wilshire Blvd,Suite 300, Beverly Hills, CA 90211 USA. EM agus@usc.edu NR 10 TC 3 Z9 3 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 J9 NAT PHYS JI Nat. Phys. PD NOV PY 2012 VL 8 IS 11 BP 773 EP 774 DI 10.1038/nphys2464 PG 2 WC Physics, Multidisciplinary SC Physics GA 033YG UT WOS:000310836700003 ER PT J AU Bourdette, D Gilden, D AF Bourdette, Dennis Gilden, Don TI Fingolimod and multiple sclerosis Four cautionary tales SO NEUROLOGY LA English DT Editorial Material ID ORAL FINGOLIMOD; THERAPY C1 [Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Bourdette, Dennis] Portland VA Med Ctr, MS Ctr Excellence W, Portland, OR USA. [Gilden, Don] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA. [Gilden, Don] Univ Colorado, Sch Med, Dept Microbiol, Aurora, CO USA. RP Bourdette, D (reprint author), Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. EM bourdett@ohsu.edu NR 12 TC 18 Z9 18 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2012 VL 79 IS 19 BP 1942 EP 1943 DI 10.1212/WNL.0b013e3182735edf PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 032US UT WOS:000310745200007 PM 23035058 ER PT J AU Tsuang, D Leverenz, JB Lopez, OL Hamilton, RL Bennett, DA Schneider, JA Buchman, AS Larson, EB Crane, PK Kaye, JA Kramer, P Woltjer, R Kukull, W Nelson, PT Jicha, GA Neltner, JH Galasko, D Masliah, E Trojanowski, JQ Schellenberg, GD Yearout, D Huston, H Fritts-Penniman, A Mata, IF Wan, JY Edwards, KL Montine, TJ Zabetian, CP AF Tsuang, Debby Leverenz, James B. Lopez, Oscar L. Hamilton, Ronald L. Bennett, David A. Schneider, Julie A. Buchman, Aron S. Larson, Eric B. Crane, Paul K. Kaye, Jeffrey A. Kramer, Patricia Woltjer, Randy Kukull, Walter Nelson, Peter T. Jicha, Gregory A. Neltner, Janna H. Galasko, Doug Masliah, Eliezer Trojanowski, John Q. Schellenberg, Gerard D. Yearout, Dora Huston, Haley Fritts-Penniman, Allison Mata, Ignacio F. Wan, Jia Y. Edwards, Karen L. Montine, Thomas J. Zabetian, Cyrus P. TI GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology SO NEUROLOGY LA English DT Article ID GAUCHER-DISEASE; GLUCOCEREBROSIDASE MUTATIONS; PARKINSONS-DISEASE; DEMENTIA; DISORDERS; NEUROPATHOLOGY; ASSOCIATION; CONSORTIUM; DIAGNOSIS; BODIES AB Objectives: Mutations in the GBA gene occur in 7% of patients with Parkinson disease (PD) and are a well-established susceptibility factor for PD, which is characterized by Lewy body disease (LBD) neuropathologic changes (LBDNCs). We sought to determine whether GBA influences risk of dementia with LBDNCs, Alzheimer disease (AD) neuropathologic changes (ADNCs), or both. Methods: We screened the entire GBA coding region for mutations in controls and in subjects with dementia and LBDNCs and no or low levels of ADNCs (pure dementia with Lewy bodies [pDLB]), LBDNCs and high-level ADNCs (LBD-AD), and high-level ADNCs but without LBDNCs (AD). Results: Among white subjects, pathogenic GBA mutations were identified in 6 of 79 pDLB cases (7.6%), 8 of 222 LBD-AD cases (3.6%), 2 of 243 AD cases (0.8%), and 3 of 381 controls (0.8%). Subjects with pDLB and LBD-AD were more likely to carry mutations than controls (pDLB: odds ratio [OR] = 7.6; 95% confidence interval [CI] = 1.8-31.9; p = 0.006; LBD-AD: OR = 4.6; CI = 1.2-17.6; p = 0.025), but there was no significant difference in frequencies between the AD and control groups (OR = 1.1; CI = 0.2-6.6; p = 0.92). There was a highly significant trend test across groups (chi(2)(1) = 19.3; p = 1.1 x 10(-5)), with the likelihood of carrying a GBA mutation increasing in the following direction: control/AD < LBD-AD < pDLB. Conclusions: GBA is a susceptibility gene across the LBD spectrum, but not in AD, and appears to convey a higher risk for PD and pDLB than for LBD-AD. PD and pDLB might be more similar to one another in genetic determinants and pathophysiology than either disease is to LBD-AD. Neurology (R) 2012;79:1944-1950 C1 [Tsuang, Debby; Leverenz, James B.; Yearout, Dora; Huston, Haley; Fritts-Penniman, Allison; Mata, Ignacio F.; Zabetian, Cyrus P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Tsuang, Debby; Leverenz, James B.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Leverenz, James B.; Yearout, Dora; Huston, Haley; Fritts-Penniman, Allison; Mata, Ignacio F.; Zabetian, Cyrus P.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Larson, Eric B.; Crane, Paul K.] Univ Washington, Dept Med, Seattle, WA USA. [Kukull, Walter; Wan, Jia Y.; Edwards, Karen L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Montine, Thomas J.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Hamilton, Ronald L.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Bennett, David A.; Buchman, Aron S.] Rush Univ, Dept Neurol Sci, Chicago, IL 60612 USA. [Schneider, Julie A.] Rush Univ, Dept Pathol, Chicago, IL 60612 USA. [Larson, Eric B.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA. [Kaye, Jeffrey A.; Kramer, Patricia] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Woltjer, Randy] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Nelson, Peter T.; Jicha, Gregory A.; Neltner, Janna H.] Univ Kentucky, Dept Pathol, Lexington, KY 40506 USA. [Jicha, Gregory A.] Univ Kentucky, Dept Neurol, Lexington, KY 40506 USA. [Galasko, Doug] Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. [Masliah, Eliezer] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Trojanowski, John Q.; Schellenberg, Gerard D.] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Trojanowski, John Q.] Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. RP Zabetian, CP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. EM dwt1@uw.edu; zabetian@u.washington.edu RI Crane, Paul/C-8623-2014; Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Fernandez Mata, Ignacio/0000-0003-1198-0633; Kaye, Jeffrey/0000-0002-9971-3478; Kukull, Walter/0000-0001-8761-9014; Crane, Paul/0000-0003-4278-7465; Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs [1I01BX000531]; National Institutes of Health [P30 AG008017, P30 AG028383, P30 AG010124, P30 AG010161, P50 AG005131, P50 NS062684, P50 AG005136, P50 AG005133, R01 AG007584, R01 AG010845, R01 AG015819, R01 AG017917, R01 NS048595, R01 NS065070, U01 AG006781, U01 AG016976]; NARSAD; American Parkinson Disease Association; Michael J. Fox Foundation; Northwest Collaborative Care; Danone Research B.V.; Illinois Department of Public Health; Robert C. Borwell Endowment Fund; Avid Radiopharmaceuticals, Inc.; Alzheimer's Association; Johnson Johnson; Roche; Bristol Myers Squibb; Pfizer; Elan Corporation; Janssen; Medivation, Inc.; Danone; NIH/NIA; National Institute on Aging; Takeda Pharmaceutical Company, Ltd.; NIH (NIA, NINDS); Marian S. Ware Alzheimer Program; Integra-Gen; NIH (NIA, NIMH); Autism Genome Project; Autism Speaks; CurePSP; Rainwater Foundation; Peebler PSP Research Foundation; Parkinson's Disease Foundation FX Supported by grants from the Department of Veterans Affairs (1I01BX000531) and the National Institutes of Health (P30 AG008017, P30 AG028383, P30 AG010124, P30 AG010161, P50 AG005131, P50 NS062684, P50 AG005136, P50 AG005133, R01 AG007584, R01 AG010845, R01 AG015819, R01 AG017917, R01 NS048595, R01 NS065070, U01 AG006781, and U01 AG016976).; D. Tsuang is funded by grants from Department of Veterans Affairs, NARSAD, and NIH. J. Leverenz has served as a consultant for Bayer and Teva Pharmaceuticals and is funded by grants from the American Parkinson Disease Association, Michael J. Fox Foundation, NIH, and Northwest Collaborative Care. O. Lopez is funded by the NIH. R. Hamilton performs diagnostic neuropathology (40% effort) and bills for these procedures. He is partly supported by grants from the NIH. D. Bennett serves on the editorial board of Neurology (R); serves on the scientific advisory board for Vigorous Minds; serves/has served as a consultant to Danone Research B. V., Willmar Schwabe GmbH, Eli Lilly, and Gerson Lehrman Group; and receives research support from Danone Research B.V., the NIH, the Illinois Department of Public Health, and the Robert C. Borwell Endowment Fund. J. Schneider served on a scientific advisory board for GE Healthcare; serves as a consultant for Avid Radiopharmaceuticals, Inc.; and receives research support from Avid Radiopharmaceuticals, Inc. and the NIH. A. Buchman is funded by the NIH. E. Larson receives research support from the NIH. P. Crane is funded by grants from the Alzheimer's Association and NIH. J. Kaye receives research support from the Department of Veterans Affairs and the NIH. Individuals who work in the research centers he directs receive research support from Johnson & Johnson, Roche, and Bristol Myers Squibb. Dr. Kaye is compensated for serving on a data monitoring committee for Eli Lilly; he serves as a paid advisor for Janssen Pharmaceutical. Dr. Kaye receives reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients; is salaried to see patients at the Portland VA Medical Center; and serves as an unpaid Vice-Chair for the International Professional Interest Area Work Group of the International Society to Advance Alzheimer's Research and Treatments (ISTAART) and as an unpaid Commissioner for the Center for Aging Services and Technologies. P. Kramer reports no disclosures. R. Woltjer is funded by the NIH. W. Kukull is funded by grants from the Alzheimer's Association and NIH. P. Nelson is funded by grants from the NIH. G. Jicha serves as a consultant for Pfizer and Eli Lilly, and receives research support from Pfizer, Elan Corporation, Janssen, Medivation, Inc., Danone, and the NIH/NIA. J. Neltner reports no disclosures. D. Galasko serves on safety monitoring committees for clinical trials for Janssen Pharmaceuticals, Elan Pharmaceuticals, and Balance Pharmaceuticals, and has served as a paid advisor to Elan Pharmaceuticals, Phloronol, Inc., and United BioSource. He has received research funding from the National Institute on Aging. E. Masliah is funded by grants from the NIH. J. Trojanowski has received funding for travel and honoraria from Takeda Pharmaceutical Company, Ltd.; ; has received speaker honoraria from Pfizer; may accrue revenue on patents regarding modified avidinbiotin technique, method of stabilizing microtubules to treat Alzheimer disease, method of detecting abnormally phosphorylated tau, method of screening for Alzheimer disease or disease associated with the accumulation of paired helical filaments, compositions and methods for producing and using homogeneous neuronal cell transplants, rat comprising straight filaments in its brain, compositions and methods for producing and using homogeneous neuronal cell transplants to treat neurodegenerative disorders and brain and spinal cord injuries, diagnostic methods for Alzheimer disease by detection of multiple MRNAs, methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases, compositions and methods for producing and using homogeneous neuronal cell transplants, method of identifying, diagnosing and treating alpha-synuclein positive neurodegenerative disorders, mutation-specific functional impairments in distinct tau isoforms of hereditary frontotemporal dementia and parkinsonism linked to chromosome-17: genotype predicts phenotype, microtubule stabilizing therapies for neurodegenerative disorders, and treatment of Alzheimer and related diseases with an antibody; and receives research support from the NIH (NIA, NINDS) and from the Marian S. Ware Alzheimer Program. G. Schellenberg serves on a scientific advisory board and receives honoraria from the American Health Assistance Foundation; has served as a consultant for and received funding for travel from Integra-Gen; holds/has filed patents regarding chromosome 14 and familial Alzheimer disease genetic markers and assays, chromosome 1 gene and gene products related to Alzheimer disease, and genetic basis of Alzheimer disease and diagnosis and treatment thereof; and receives/has received research support from the NIH (NIA, NIMH), the Autism Genome Project, Autism Speaks, CurePSP, the Rainwater Foundation, and Peebler PSP Research Foundation. He is an uncompensated member (other than travel funds to meetings of these boards) of the Alzheimer's Association Medical and Scientific Advisory Council, CSP #546 Executive Committee, Veterans Affairs Dementia Prevention Study of Vitamin E and Memantine, the Board of the Peebler PSP Research Foundation, and the Medical Advisory Board, Society of Progressive Supranuclear Palsy. D. Yearout and H. Huston receive salary support from the Department of Veterans Affairs and NIH. A. Fritts-Penniman received salary support from the Department of Veterans Affairs and NIH. I. Mata is funded by grants from the Department of Veterans Affairs, NIH, and Parkinson's Disease Foundation. J. Wan receives salary support from the Department of Veterans Affairs and NIH. K. Edwards and T. Montine are funded by grants from the NIH. C. Zabetian is funded by grants from the American Parkinson Disease Association, Department of Veterans Affairs, NIH, Northwest Collaborative Care, and Parkinson's Disease Foundation. Go to Neurology.org for full disclosures. NR 26 TC 50 Z9 50 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2012 VL 79 IS 19 BP 1944 EP 1950 DI 10.1212/WNL.0b013e3182735e9a PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 032US UT WOS:000310745200008 PM 23035075 ER PT J AU Levy-Gigi, E Keri, S Myers, CE Lencovsky, Z Sharvit-Benbaji, H Orr, SP Gilbertson, MW Servatius, RJ Tsao, JW Gluck, MA AF Levy-Gigi, Einat Keri, Szabolcs Myers, Catherine E. Lencovsky, Zvi Sharvit-Benbaji, Hadas Orr, Scott P. Gilbertson, Mark W. Servatius, Richard J. Tsao, Jack W. Gluck, Mark A. TI Individuals With Posttraumatic Stress Disorder Show a Selective Deficit in Generalization of Associative Learning SO NEUROPSYCHOLOGY LA English DT Article DE PTSD; learning; hippocampus; generalization ID COGNITIVE-BEHAVIORAL THERAPY; SMALLER HIPPOCAMPAL VOLUME; IDENTICAL-TWINS DISCORDANT; CHILDHOOD SEXUAL-ABUSE; ACQUIRED EQUIVALENCE; PSYCHIATRIC-DISORDERS; INHIBITED TEMPERAMENT; PSYCHOLOGICAL TRAUMA; DECLARATIVE MEMORY; COMBAT EXPOSURE AB Objective: Drawing on two different populations, Israeli police and Hungarian civilians, the present study assessed the ability of individuals with posttraumatic stress disorder (PTSD) to generalize previous learning to novel situations. Past neuroimaging studies have demonstrated diminished medial temporal lobe (MTL) activation and/or reduced hippocampal volume in individuals with PTSD. Our earlier computational models of cortico-hippocampal function and subsequent experimental tests of these models in MTL-impaired clinical populations argue that even mild hippocampal dysfunction may result in subtle impairments in generalization. Therefore, we predicted that individuals with PTSD would show impaired generalization. Method: We compared the performance of five groups from two countries, including 19 Israeli police with PTSD and 22 trauma-exposed police without PTSD, and 22 Hungarian civilians with PTSD, 25 trauma-exposed civilians without PTSD, and 25 individuals without PTSD unexposed to the same trauma. Participants were tested on a two-phase learning paradigm, the Acquired Equivalence Task, which measures the ability to generalize past learning to novel situations. Results: We found that both PTSD and non-PTSD participants were capable of learning the initial stimulus-outcome associations, F(4, 108) = 1.79, p = .14. However, as predicted, only individuals with PTSD showed a selective deficit in generalization of this learning to novel situations (F(4, 108) = 8.35, p < .001, Partial eta(2) = 0.26). Conclusions: Individuals with PTSD show a selective impairment in generalization of past learning similar to other clinical populations with MTL/hippocampal dysfunction. This is consistent with an emerging view of PTSD as being not only an anxiety disorder but also a learning disorder. C1 [Levy-Gigi, Einat; Gluck, Mark A.] Rutgers State Univ, Newark, NJ 07102 USA. [Keri, Szabolcs] Univ Szeged, Dept Physiol, Fac Med, Szeged, Hungary. [Keri, Szabolcs] Natl Psychiat Ctr, Budapest, Hungary. [Myers, Catherine E.; Servatius, Richard J.] New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ USA. [Myers, Catherine E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ 07103 USA. [Lencovsky, Zvi; Sharvit-Benbaji, Hadas] Israel Police, Jerusalem, Israel. [Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Orr, Scott P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gilbertson, Mark W.] Dept Vet Affairs, Manchester, NH USA. [Servatius, Richard J.] Univ Med & Dent UMDNJ, Grad Sch Biomed Sci, Newark, NJ USA. [Servatius, Richard J.] Stress & Motivated Behav Inst SMBI, VA, E Orange, NJ USA. [Tsao, Jack W.] USN, Bur Med & Surg BUMED, Washington, DC USA. RP Levy-Gigi, E (reprint author), 197 Univ Ave, Newark, NJ 07102 USA. EM levygigie@gmail.com OI Myers, Catherine/0000-0002-2776-4823 NR 76 TC 20 Z9 20 U1 4 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2012 VL 26 IS 6 BP 758 EP 767 DI 10.1037/a0029361 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 030GL UT WOS:000310558800009 PM 22846034 ER PT J AU Walcott, BP Redjal, N Coumans, JVCE AF Walcott, Brian P. Redjal, Navid Coumans, Jean-Valery C. E. TI Infection following operations on the central nervous system: deconstructing the myth of the sterile field SO NEUROSURGICAL FOCUS LA English DT Article DE infection; complication; normothermia; hyperglycemia; irrigation; dressing; antibiotic; bandage; obesity; oxygen; glove; sterile; microbiome; nutrition ID SURGICAL SITE INFECTION; RANDOMIZED CONTROLLED-TRIAL; SUPPLEMENTAL PERIOPERATIVE OXYGEN; ENHANCING NUTRITIONAL SUPPLEMENT; PREOPERATIVE WEIGHT-LOSS; WOUND-INFECTION; CARDIAC-SURGERY; MEDIAN STERNOTOMY; POSTOPERATIVE INFECTIONS; ANTIBIOTIC-PROPHYLAXIS AB Neurosurgical patients are at a high risk for infectious sequelae following operations. For neurosurgery in particular, the risk of surgical site infection has a unique implication given the proximity of the CSF and the CNS. Patient factors contribute to some degree; for example, cancer and trauma are often associated with impaired nutritional status, known risk factors for infection. Additionally, care-based factors for infection must also be considered, such as the length of surgery, the administration of steroids, and tissue devascularization (such as a craniotomy bone flap). When postoperative infection does occur, attention is commonly focused on potential lapses in surgical "sterility." Evidence suggests that the surgical field is not free of microorganisms. The authors propose a paradigm shift in the nomenclature of the surgical field from "sterile" to "clean." Continued efforts aimed at optimizing immune capacity and host defenses to combat potential infection are warranted. (http://thejns.org/doi/abs/10.3171/2012.8.FOCUS12245) C1 [Walcott, Brian P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walcott, BP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,White Bldg,Room 502, Boston, MA 02114 USA. EM walcott.brian@mgh.harvard.edu FU Council of State Neurological Societies Socioeconomic Fellowship FX Dr. Walcott is supported by the Council of State Neurological Societies Socioeconomic Fellowship (2012-2013). NR 110 TC 9 Z9 10 U1 0 U2 13 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1092-0684 J9 NEUROSURG FOCUS JI Neurosurg. Focus PD NOV PY 2012 VL 33 IS 5 AR E8 DI 10.3171/2012.8.FOCUS12245 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 031GT UT WOS:000310628100009 PM 23116103 ER PT J AU Bae, S Jung, JH An, IS Kim, OY Lee, MJ Lee, JH Park, IC Lee, SJ An, S AF Bae, Seunghee Jung, Jin Hyuk An, In-Sook Kim, Ok-Yeoun Lee, Myoung Joo Lee, Jae Ho Park, In-Chul Lee, Su-Jae An, Sungkwan TI TRIAD1 is negatively regulated by the MDM2 E3 ligase SO ONCOLOGY REPORTS LA English DT Article DE p53; murine double minute 2; ubiquitination; two RING fingers and DRIL1 ID UBIQUITIN-PROTEIN LIGASE; LOCUS DELETION; P53; DEGRADATION; EXPRESSION; PATHWAY; SYSTEM; CANCER; CELLS; ARF AB Two RING fingers and DRIL1 (TRIAD1) is a proapoptotic protein that promotes p53 activation in several cancer cell lines, including MCF7, U2OS and A549 cells. In this study, we demonstrated that TRIAD1 is a novel ubiquitination target for proteasome-dependent degradation by murine double minute 2 (MDM2). TRIAD1 was found to interact with and be ubiquitinated by MDM2. RNA interference against MDM2 increased endogenous TRIAD1 protein stability. The functional study results suggested that TRIAD1 degradation by MDM2 suppresses TRIAD1-mediated cell growth. These data suggested a novel negative regulatory mechanism of TRIAD1 via MDM2 E3 ligase ubiquitination. C1 [Bae, Seunghee; Jung, Jin Hyuk; An, Sungkwan] Konkuk Univ, Mol Targeted Drug Res Ctr, Seoul 143701, South Korea. [Jung, Jin Hyuk] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Dev & Stem Cell Biol,Dept Med, Boston, MA 02215 USA. [An, In-Sook; Kim, Ok-Yeoun; Lee, Myoung Joo] Konkuk Univ, Korea Inst Skin & Clin Sci, Seoul 143701, South Korea. [Lee, Jae Ho] Kwandong Univ, Coll Med, Cheil Gen Hosp, Mol Oncol Lab, Seoul 100380, South Korea. [Lee, Jae Ho] Kwandong Univ, Coll Med, Womens Healthcare Ctr, Seoul 100380, South Korea. [Park, In-Chul] Korea Inst Radiol & Med Sci, Lab Funct Genom, Seoul 139706, South Korea. [Lee, Su-Jae] Hanyang Univ, Dept Chem, Seoul 133791, South Korea. RP An, S (reprint author), Konkuk Univ, Mol Targeted Drug Res Ctr, 1 Hwayang Dong, Seoul 143701, South Korea. EM ansfgrc@konkuk.ac.kr FU Konkuk University FX The authors would like to thank Dr B.A. van der Reijden (Radboud University Nijmegen Medical Centre, The Netherlands), for providing the GFP-TRIAD1 plasmids. The authors are also grateful to the members of the research group, for their support and suggestions regarding this study. The present study was financed by the 2011 Konkuk University research support program. NR 18 TC 3 Z9 3 U1 0 U2 3 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD NOV PY 2012 VL 28 IS 5 BP 1924 EP 1928 DI 10.3892/or.2012.2005 PG 5 WC Oncology SC Oncology GA 031QV UT WOS:000310657900056 PM 22940738 ER PT J AU Jakobiec, FA Zakka, FR Papakostas, TD Fay, A AF Jakobiec, Frederick A. Zakka, Fouad R. Papakostas, Thanos D. Fay, Aaron TI Angiomyofibroma of the Orbit: A Hybrid of Vascular Leiomyoma and Cavernous Hemangioma SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID JUVENILE NASOPHARYNGEAL ANGIOFIBROMA; LEIOMYOSARCOMA; MUSCLE; DESMIN; DIFFERENTIATION; MYOFIBROBLAST; MALFORMATIONS; ENOPHTHALMOS; INVOLVEMENT; CARCINOMA AB Purpose: The aim of this study was to describe a novel primary orbital vascular tumor combining elements of a vascular leiomyoma (angioleiomyoma) and a cavernous hemangioma. Methods: A critical review of clinical records, diagnostic tests, and radiographic studies combined with histopathologic evaluation with standard and special histochemical staining and immunohistochemical investigations was conducted. Results: A 44-year-old man slowly developed 5 mm of well-tolerated relative right proptosis with minimal motility disturbance and no visual decline. Computed tomography and magnetic resonance imaging demonstrated a medial and intraconal rounded mass that perfused slowly and whose anterior surface was well circumscribed. At surgery, the tumor was solid and pink with intersecting white bands and densely attached to surrounding normal tissues. The most adherent apical portion of the mass was left behind after subtotal excision. Histopathologically, only a partial pseudocapsule was discovered. The tumor was composed of cavernous channels, capillary zones, compressed lumens with linear strands of endothelium, and collections of muscular veins devoid of an elastica. Striking smooth muscle actin positivity was identified in disorganized masses of smooth muscle cells in the intervascular spaces and around the cavernous vascular units; these myocytes were intermixed with bundles of interstitial keloidal collagen. The endothelium was CD31 and CD34 positive for vascular endothelium and D2-40 negative for lymphatic endothelium. Conclusions: The authors have classified this hybrid tumor an angiomyofibroma with low neoplastic potential and features of a malformation. It is a composite variant of cavernous hemangioma associated with a conspicuous proliferation of anomalous disorganized smooth muscle cells (leiomyoma). Most of the lesion lacked a pseudocapsule, which impeded surgical delivery. Incomplete excision is recommended in such cases as preferable to the complications that could ensue from overly aggressive efforts at complete removal, particularly at the orbital apex. Supporting this position is the observation that incompletely excised cavernous hemangioma generally does not recur. (Ophthal Plast Reconstr Surg 2012;28:438-445) C1 [Jakobiec, Frederick A.; Zakka, Fouad R.; Papakostas, Thanos D.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Boston, MA 02114 USA. [Fay, Aaron] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Oculoplast Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Lab Ophthalm Pathol,Dept Ophthalmol, Suite 321,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 56 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2012 VL 28 IS 6 BP 438 EP 445 DI 10.1097/IOP.0b013e318269693e PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 037BE UT WOS:000311075200025 PM 23138203 ER PT J AU Callahan, AB Jakobiec, FA Zakka, FR Fay, A AF Callahan, Alison B. Jakobiec, Frederick A. Zakka, Fouad R. Fay, Aaron TI Isolated Unilateral Linear Epidermal Nevus of the Upper Eyelid SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MANIFESTATIONS AB A 75-year-old man presented with a recurrent, unilateral, solitary, linear, corrugated lesion of the right upper eyelid of prolonged duration together with bilateral dermatochalasis. A re-excision with blepharoplasty was performed. Histopathologic analysis of the tissue revealed parallel linear arrays of papillomatosis and acanthosis with overlying basket-weave hyperkeratosis consistent with a linear epidermal nevus. Immunohistochemical studies disclosed normal numbers of intraepidermal melanocytes and Langerhans cells without Merkel cells or an increase in cycling keratinocytes. Although the term "nevus" is mostly used in conjunction with the common nevomelanocytic nevus, in fact nevi of other cutaneous cellular elements can occur on a malformational basis (such as sebaceous, eccrine, apocrine, pilar, and elastic fiber nevi). Ophthalmologists should be aware of epidermal nevi because they are rarely associated with cataracts, malignant cutaneous neoplasms, neurologic abnormalities, and musculoskeletal disorders. For focal lesions like the present one, local excision is appropriate. A select differential diagnosis of histopathologically related conditions is provided. C1 [Callahan, Alison B.; Jakobiec, Frederick A.; Zakka, Fouad R.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, Boston, MA 02114 USA. [Fay, Aaron] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Div Oculoplast Surg, Boston, MA 02114 USA. [Fay, Aaron] Harvard Univ, Sch Med, Boston, MA USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, David G Cogan Lab Ophthalm Pathol, 243 Charles St,Suite 321, Boston, MA 02114 USA. EM fred_jakobiec@meei.harvard.edu NR 22 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV-DEC PY 2012 VL 28 IS 6 BP E135 EP E138 DI 10.1097/IOP.0b013e318248e66e PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 037BE UT WOS:000311075200003 PM 22460676 ER PT J AU Elman, MJ Qin, HJ Aiello, LP Beck, RW Bressler, NM Ferris, FL Glassman, AR Maturi, RK Melia, M AF Elman, Michael J. Qin, Haijing Aiello, Lloyd Paul Beck, Roy W. Bressler, Neil M. Ferris, Frederick L., III Glassman, Adam R. Maturi, Raj K. Melia, Michele CA Diabetic Retinopathy Clinical Res TI Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred Laser Treatment Three-Year Randomized Trial Results SO OPHTHALMOLOGY LA English DT Article ID PLUS PROMPT AB Objective: To report the 3-year follow-up results within a previously reported randomized trial evaluating prompt versus deferred (for >= 24 weeks) focal/grid laser treatment in eyes treated with intravitreal 0.5 mg ranibizumab for diabetic macular edema (DME). Design: Multicenter, randomized clinical trial. Participants: Three hundred sixty-one participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Methods: Ranibizumab every 4 weeks until no longer improving (with resumption if worsening) and random assignment to prompt or deferred (>= 24 weeks) focal/grid laser treatment. Main Outcome Measures: Best-corrected visual acuity and safety at the 156-week (3-year) visit. Results: The estimated mean change in visual acuity letter score from baseline through the 3-year visit was 2.9 letters more (9.7 vs. 6.8 letters; mean difference, 2.9 letters; 95% confidence interval, 0.4-5.4 letters; P = 0.02) in the deferral group compared with the prompt laser treatment group. In the prompt laser treatment group and deferral group, respectively, the percentage of eyes with a >= 10-letter gain/loss was 42% and 56% (P = 0.02), whereas the respective percentage of eyes with a >= 10-letter gain/loss was 10% and 5% (P = 0.12). Up to the 3-year visit, the median numbers of injections were 12 and 15 in the prompt and deferral groups, respectively (P = 0.007), including 1 and 2 injections, respectively, from the 2-year up to the 3-year visit. At the 3-year visit, the percentages of eyes with central subfield thickness of 250 mu m or more on time-domain optical coherence tomography were 36% in both groups (P = 0.90). In the deferral group, 54% did not receive laser treatment during the trial. Systemic adverse events seemed to be similar in the 2 groups. Conclusions: These 3-year results suggest that focal/grid laser treatment at the initiation of intravitreal ranibizumab is no better, and possibly worse, for vision outcomes than deferring laser treatment for 24 weeks or more in eyes with DME involving the fovea and with vision impairment. Some of the observed differences in visual acuity at 3 years may be related to fewer cumulative ranibizumab injections during follow-up in the prompt laser treatment group. Follow-up through 5 years continues. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012;119:2312-2318 (C) 2012 by the American Academy of Ophthalmology. C1 [Qin, Haijing; Beck, Roy W.; Glassman, Adam R.; Melia, Michele] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA. [Elman, Michael J.] Elman Retina Grp, Baltimore, MD USA. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst,Dept Ophthalmol, Boston, MA 02115 USA. [Bressler, Neil M.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. [Ferris, Frederick L., III] NEI, NIH, Bethesda, MD 20892 USA. RP Qin, HJ (reprint author), Jaeb Ctr Hlth Res, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrstat3@jaeb.org FU National Eye Institute; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland [EY14231, EY14229, EY18817]; Genentech; Office of Research Administration; Abbott Medical Optics; Allergan; Bausch Lomb; Bristol-Meyer-Squibb; Carl Zeiss Meditec; EMMES Corporation; ForSight Labs; LLC Genentech; Genzyme Corporation; Lumenis; Notal Vision; Novartis; Regeneron FX Supported through cooperative agreements from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland (grant nos.: EY14231, EY14229, and EY18817).; The funding organization (National Institutes of Health) participated in oversight of the conduct of the study and review of the manuscript, but not directly in the design or conduct of the study; nor in the collection, management, analysis, or interpretation of the data; nor in the preparation of the manuscript. Genentech provided the ranibizumab for the study. In addition, Genentech provided funds to DRCR.net to defray the study's clinical site costs. As described in the Diabetic Retinopathy Clinical Research Network (DRCR.net) Industry Collaboration Guidelines (available at www.drcr.net), the DRCR.net had complete control over the design of the protocol, ownership of the data, and all editorial content of presentations and publications related to the protocol. A complete list of all DRCR.net investigator financial disclosures can be found at www.drcr.net. Writing Committee financial disclosures: Neil M. Bressler: Grants to investigators at The Johns Hopkins University are negotiated and administered by the institution (such as the School of Medicine), which receives the grants, typically through the Office of Research Administration. Individual investigators who participate in the sponsored project(s) are not compensated directly by the sponsor, but may receive salary or other support from the institution to support their effort on the projects(s). Neil M. Bressler is the principal investigator of grants at The Johns Hopkins University sponsored by the following entities (not including the National Institutes of Health): Abbott Medical Optics, Allergan, Bausch & Lomb, Bristol-Meyer-Squibb, Carl Zeiss Meditec, EMMES Corporation, ForSight Labs, LLC Genentech, Genzyme Corporation, Lumenis, Notal Vision, Novartis, and Regeneron. A complete list of all DRCR. net investigator financial disclosures can be found at www.drcr.net. NR 4 TC 121 Z9 126 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2012 VL 119 IS 11 BP 2312 EP 2318 DI 10.1016/j.ophtha.2012.08.022 PG 7 WC Ophthalmology SC Ophthalmology GA 030OH UT WOS:000310579500018 ER PT J AU Daniel, E Pistilli, M Pujari, SS Kacmaz, RO Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE Foster, CS Jabs, DA Levy-Clarke, GA Kempen, JH AF Daniel, Ebenezer Pistilli, Maxwell Pujari, Siddharth S. Kacmaz, R. Oktay Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Kempen, John H. TI Risk of Hypotony in Noninfectious Uveitis SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; OCULAR COMPLICATIONS; CYTOMEGALOVIRUS RETINITIS; ULTRASOUND BIOMICROSCOPY; CYCLODIALYSIS CLEFT; CATARACT-SURGERY; PHACOEMULSIFICATION; PRESSURE; MACULOPATHY; VITRECTOMY AB Objective: We sought to describe the risk and risk factors for hypotony in a noninfectious uveitis cohort. Design: Retrospective cohort study. Participants: Patients with noninfectious uveitis seen between 1979 and 2007 at 4 academic ocular inflammation specialty clinics. Methods: Data were collected from medical records by trained, certified, expert reviewers. Main Outcome Measures: Hypotony (<5 mmHg) and low intraocular pressure (<8 mmHg), each sustained for >= 2 visits spanning >= 30 days. Results: During follow-up, 126 of 6785 patients (1.86%) developed hypotony at the rate of 0.61% (95% confidence interval [CI], 0.50-0.75%) per eye-year. Cataract surgery was associated with a 7.5-fold risk (adjusted hazard ratio [aHR], 7.51; 95% CI, 3.97-14.23) of incident hypotony. Phacoemulsification, the type of cataract surgery associated with the least hypotony risk still was associated with nearly 5-fold higher hypotony incidence (aHR, 4.87; 95% CI, 2.25-10.55). Increased risk was observed in children (aHR, 2.92; 95% CI, 1.20-7.10) with respect to young adults, and duration of uveitis of >5 years (aHR, 3.08; 95% CI, 1.30-7.31) with respect to uveitis of <6 month duration. Band keratopathy, >= 3+ vitreous cells, exudative retinal detachment, posterior synechia, and a history of pars plana vitrectomy also were associated with greater hypotony incidence. With respect to anterior uveitis, intermediate uveitis (aHR, 0.17; 95% CI, 0.05-0.56) and posterior uveitis (aHR, 0.11; 95% CI, 0.03-0.45) were associated with lower hypotony risk, whereas panuveitis (aHR, 1.25; 95% CI, 0.67-2.35) was similar. Approximately five-sixths (84.1%) of eyes presenting with hypotony had a visual acuity of <20/200 (aOR for visual acuity <20/200, 13.85; 95% CI, 7.23-26.53). Risk factors for prevalent hypotony were similar. Conclusions: The risk of hypotony is low among eyes with noninfectious uveitis, but is more frequently observed in cases with anterior segment inflammation. Signs of present or past inflammation were associated with greater risk, suggesting excellent inflammatory control may reduce the risk of hypotony. Prior ocular surgery also was associated with higher risk; cataract surgery in particular was associated with much higher risk of hypotony. Lower risk of hypotony with phacoemulsification than with alternative cataract surgery approaches suggests the phacoemulsification approach is preferable. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. Ophthalmology 2012; 119: 2377-2385 (C) 2012 by the American Academy of Ophthalmology. C1 [Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, Philadelphia, PA 19104 USA. [Daniel, Ebenezer; Pistilli, Maxwell; Kempen, John H.] Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Pujari, Siddharth S.; Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Pujari, Siddharth S.] Lions Nab Eye Hosp, Miraj, Maharashtra, India. [Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA USA. [Nussenblatt, Robert B.; Levy-Clarke, Grace A.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. [Thorne, Jennifer E.] Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. [Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA. EM john.kempen@uphs.upenn.edu OI Daniel, Ebenezer/0000-0002-2027-2316; Pistilli, Maxwell/0000-0002-4266-4150 FU National Eye Institute [EY014943]; Research to Prevent Blindness (RPB); Paul and Evanina Mackall Foundation FX This study was supported primarily by National Eye Institute Grant EY014943 (J.H.K.). Additional support was provided by Research to Prevent Blindness (RPB) and the Paul and Evanina Mackall Foundation. J.H.K. was an RPB James S. Adams Special Scholar Award recipient, J.E.T. was an RPB Harrington Special Scholar Award recipient, and D.A.J. and J.T.R. were Research to Prevent Blindness Senior Scientific Investigator Award recipients during the course of the study. G. A. L.-C. was previously supported by and R.B.N. continues to be supported by intramural funds of the National Eye Institute. E. B. S. receives support from the Department of Veterans' Affairs. None of the sponsors had any role in the design and conduct of the report; collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of this manuscript. NR 25 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 2012 VL 119 IS 11 BP 2377 EP 2385 DI 10.1016/j.ophtha.2012.05.032 PG 9 WC Ophthalmology SC Ophthalmology GA 030OH UT WOS:000310579500027 PM 22796306 ER PT J AU Cohen-Adad, J Buchbinder, B Oaklander, AL AF Cohen-Adad, Julien Buchbinder, Bradley Oaklander, Anne Louise TI Cervical spinal cord injection of epidural corticosteroids: Comprehensive longitudinal study including multiparametric magnetic resonance imaging SO PAIN LA English DT Article DE Adverse event; Spinal cord injury; Wallerian degeneration; Diffusion tensor imaging; Magnetization transfer; Central motor conduction time ID MULTIPLE-SCLEROSIS; WALLERIAN DEGENERATION; WHITE-MATTER; AXONAL INJURY; CLINICAL-APPLICATIONS; STEROID INJECTIONS; MOUSE MODEL; BRAIN; MYELIN; NERVE AB Despite widespread use, the efficacy of epidural corticosteroid injections (ESI) for osteoarthritis-associated neck or radicular pain remains uncertain, so even rare serious complications enter into discussions about use. However, various factors impede investigation and publication of serious adverse events. To that end, we developed new magnetic resonance imaging (MRI) techniques for spinal cord white matter quantification and used the best available physiological tests to characterize a cervical spinal cord lesion caused by inadvertent intramedullary injection of Depo-Medrol. A 29-year-old woman with mild cervical osteoarthritis had 2 years of headache and neck pain (concussion and whiplash) after 2 minor motor vehicle accidents. During C5-6 ESI, she developed new left-sided motor and sensory symptoms, and MRI demonstrated a new left dorsal spinal cord cavity. Mild left-sided motor and sensory symptoms have persisted for more than 2.5 years, during which time we performed serial neurological examinations, standard electrodiagnostics, somatosensory evoked potentials, and transcranial measurement of cortico-spinal central motor conduction time (CMCT). We used 3-Tesla MRI with a 32-channel coil developed for high-resolution cervical spinal cord structural imaging, diffusion tensor imaging (DTI), and magnetization transfer (MT). T-2(*)-weighted signal and DTI and MT metrics showed delayed spread of the lesion across 4 vertebral levels rostrally, consistent with Wallerian degeneration within the ascending left dorsal columns. However, only CMCT metrics detected objective correlates of her left hemiparesis and bilateral hyperreflexia. DTI and MT metrics may better distinguish between post-traumatic demyelination and axonal degeneration than conventional MRI. These tests should be considered to better characterize similar spinal cord injuries. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Cohen-Adad, Julien] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3T 1J4, Canada. [Cohen-Adad, Julien] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Cohen-Adad, Julien; Buchbinder, Bradley; Oaklander, Anne Louise] Harvard Univ, Sch Med, Boston, MA USA. [Buchbinder, Bradley] Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. RP Cohen-Adad, J (reprint author), Ecole Polytech, Dept Elect Engn, 2900 Edouard Montpetit Bld, Montreal, PQ H3T 1J4, Canada. EM jcohen@polymtl.ca FU Public Health Service; National Multiple Sclerosis Society [FG 1892A1/1]; [NIH-P41RR14075]; [NIH-K24NS59892]; [NIH-1S10OD010364]; [NIH-U01MH093765] FX Funded in part by the Public Health Service; NIH-P41RR14075, NIH-K24NS59892, NIH-1S10OD010364, NIH-U01MH093765 National Multiple Sclerosis Society (FG 1892A1/1). Presented in abstract form at the 2011 meeting of the International Society for Magnetic Resonance in Medicine. We thank Dr. Lawrence Wald for helping with MRI acquisition. NR 55 TC 4 Z9 6 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2012 VL 153 IS 11 BP 2292 EP 2299 DI 10.1016/j.pain.2012.07.028 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 033CZ UT WOS:000310772400021 PM 22964435 ER PT J AU Das, KK Xiao, HD Geng, X Fernandez-del-Castillo, C Morales-Oyarvide, V Forcione, DG Bounds, BC Brugge, WR Pitman, MB Das, KM Mino-Kenudson, M AF Das, K. K. Xiao, H. D. Geng, X. Fernandez-del-Castillo, C. Morales-Oyarvide, V. Forcione, D. G. Bounds, B. C. Brugge, W. R. Pitman, M. B. Das, K. M. Mino-Kenudson, M. TI mAb Das-1 Is Specific for High-Risk and Malignant Intraductal Papillary Mucinous Neoplasm (IPMN) SO PANCREAS LA English DT Meeting Abstract C1 [Das, K. K.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [Xiao, H. D.; Pitman, M. B.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Fernandez-del-Castillo, C.; Morales-Oyarvide, V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Forcione, D. G.; Bounds, B. C.; Brugge, W. R.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Geng, X.; Das, K. M.] UMDNJ Robert Wood Johnson Med Sch, Div Gastroenterol, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1354 EP 1355 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500073 ER PT J AU Liu, Y Yuan, J Tan, T Jia, W Lugea, A Gukovskaya, AS Pandol, SJ AF Liu, Y. Yuan, J. Tan, T. Jia, W. Lugea, A. Gukovskaya, A. S. Pandol, S. J. TI PKC epsilon is a Critical Mediator of Necrosis in Acute Pancreatitis by Regulation of Mitochondrial and Non-Mitochondrial Death Pathways SO PANCREAS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1380 EP 1380 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500180 ER PT J AU Mareninova, OA Yakubov, I Yuan, J Lugea, A Gukovsky, I Gukovskaya, AS AF Mareninova, O. A. Yakubov, I. Yuan, J. Lugea, A. Gukovsky, I. Gukovskaya, A. S. TI Rab Disordering in Pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1383 EP 1383 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500194 ER PT J AU Sahora, K Mino-Kenudson, M Thayer, SP Ferrone, C Wargo, J Warshaw, AL Lillemoe, K Fernandez-del Castillo, C AF Sahora, K. Mino-Kenudson, M. Thayer, S. P. Ferrone, C. Wargo, J. Warshaw, A. L. Lillemoe, K. Fernandez-del Castillo, C. TI Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasms of the Pancreas: Risk of Malignancy and Concomitant Ductal Adenocarcinoma SO PANCREAS LA English DT Meeting Abstract C1 [Sahora, K.; Thayer, S. P.; Ferrone, C.; Wargo, J.; Warshaw, A. L.; Lillemoe, K.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mino-Kenudson, M.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1399 EP 1400 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500262 ER PT J AU Sahora, K Dias-Santagata, D Morales-Oyarvide, V Bernardo, LA Iafrate, AJ Pitman, MB Fernandez-del Castillo, C Mino-Kenudson, M AF Sahora, K. Dias-Santagata, D. Morales-Oyarvide, V. Bernardo, L. A. Iafrate, A. J. Pitman, M. B. Fernandez-del Castillo, C. Mino-Kenudson, M. TI GNAS and KRAS Mutations in Multifocal Intraductal Papillary Mucinous Neoplasms (IPMN) of the Pancreas - Pilot Study SO PANCREAS LA English DT Meeting Abstract C1 [Sahora, K.; Fernandez-del Castillo, C.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Dias-Santagata, D.; Morales-Oyarvide, V.; Bernardo, L. A.; Iafrate, A. J.; Pitman, M. B.; Mino-Kenudson, M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1399 EP 1399 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500261 ER PT J AU Yamaguchi, J Mino-Kenudson, M Liss, AS Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Thayer, SP AF Yamaguchi, J. Mino-Kenudson, M. Liss, A. S. Lillemoe, K. D. Fernandez-del Castillo, C. Warshaw, A. L. Thayer, S. P. TI Pancreatic Duct Glands (PDG), a Progenitor Stem Cell Niche Responsible for Pancreatic Epithelial Renewal and Repair in Response to Inflammatory Injury SO PANCREAS LA English DT Meeting Abstract C1 [Yamaguchi, J.; Liss, A. S.; Lillemoe, K. D.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Warshaw Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1414 EP 1414 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500323 ER PT J AU Yoon, WJ Daglilar, ES Mino-Kenudson, M Morales-Oyarvide, V Pitman, MB Brugge, WR AF Yoon, W. J. Daglilar, E. S. Mino-Kenudson, M. Morales-Oyarvide, V. Pitman, M. B. Brugge, W. R. TI Epithelial Subtypes of Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: EUS and Cyst Fluid Analysis SO PANCREAS LA English DT Meeting Abstract C1 [Yoon, W. J.; Daglilar, E. S.; Brugge, W. R.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Mino-Kenudson, M.; Morales-Oyarvide, V.; Pitman, M. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2012 VL 41 IS 8 BP 1415 EP 1415 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027NV UT WOS:000310360500326 ER PT J AU Naumann, HL Haberkern, CM Pietila, KE Birgfeld, CB Starr, JR Kapp-Simon, KA Hopper, RA Speltz, ML AF Naumann, Heather L. Haberkern, Charles M. Pietila, Kristen E. Birgfeld, Craig B. Starr, Jacqueline R. Kapp-Simon, Kathleen A. Hopper, Richard A. Speltz, Matthew L. TI Duration of exposure to cranial vault surgery: associations with neurodevelopment among children with single-suture craniosynostosis SO PEDIATRIC ANESTHESIA LA English DT Article DE cranioplasty; anesthesia; neurodevelopment; infants ID LEARNING-DISABILITIES; DEVELOPING BRAIN; BIRTH COHORT; ANESTHESIA; INFANTS; TIME AB Objective: To evaluate associations between neurodevelopment and exposure to surgery and anesthetic agents in children with single-suture craniosynostosis (SSC). Background: Young children with SSC have unexplained neurodevelopmental delays. The possible contributions of factors related to cranial vault surgery - including anesthesia - have not been previously examined. Methods/materials: Two anesthesiologists reviewed the surgical records of 89 infants (70 had complete data). Primary exposures were duration of surgery and anesthesia and total duration of inhaled anesthesia (at age 6 months on average). Outcomes were the cognitive and motor scores from the Bayley Scales of Infant Development-II and language scores from the Preschool Language Scale, 3rd edition, given at age 36 months. Linear regression using robust standard error estimates was performed, adjusting for age at surgery and suture site. Results: Anesthesia duration ranged from 155 to 547 min. For every 30-min increase in anesthesia duration, the estimated average decrease in developmental test scores ranged from 1.1 to 2.9 (P ranged from < 0.001 to 0.30). Similar, but weaker findings were observed with surgery duration and total duration of inhaled anesthesia. Inverse relations between exposure amounts and neurodevelopment were stronger in children with non-sagittal synostosis. Conclusions: Average neurodevelopmental scores were lower among children experiencing longer surgeries and higher exposures to inhaled anesthesia. These associations may be due to anesthesia exposure, nonspecific effects of surgery, or unmeasured variables that correlate with surgery duration. Further study of potential causal mechanisms is warranted. C1 [Naumann, Heather L.; Haberkern, Charles M.; Birgfeld, Craig B.; Hopper, Richard A.; Speltz, Matthew L.] Seattle Childrens Hosp, Seattle, WA 98145 USA. [Naumann, Heather L.; Haberkern, Charles M.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Haberkern, Charles M.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Pietila, Kristen E.; Starr, Jacqueline R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Birgfeld, Craig B.; Hopper, Richard A.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Starr, Jacqueline R.] Forsyth Inst, Cambridge, MA USA. [Kapp-Simon, Kathleen A.] Northwestern Univ, Dept Surg, Chicago, IL 60611 USA. [Kapp-Simon, Kathleen A.] Shriners Hosp Children, Chicago, IL USA. [Speltz, Matthew L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Speltz, ML (reprint author), Seattle Childrens Hosp, 4800 Sand Point Way NE,W-3636, Seattle, WA 98145 USA. EM mspeltz@uw.edu OI Starr, Jacqueline/0000-0002-3039-2311 FU National Institute of Dental and Craniofacial Research (NIDCR) [R01 DE 13813] FX This work was supported by a grant from the National Institute of Dental and Craniofacial Research (NIDCR grant # R01 DE 13813 awarded to Dr. Speltz). We would like to acknowledge Pravin K. Patel, M.D., FACS, Professor of Surgery, Director, Craniofacial Services, Division of Plastic, Reconstructive and Cosmetic Surgery, University of Illinois at Chicago, IL, USA; Chief, Plastic Surgery Service, Shriners Hospital for Children, Chicago, IL, USA for his thoughtful review of the manuscript. NR 25 TC 9 Z9 10 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD NOV PY 2012 VL 22 IS 11 BP 1053 EP 1061 DI 10.1111/j.1460-9592.2012.03843.x PG 9 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 033MW UT WOS:000310802400003 PM 22502768 ER PT J AU Vassy, JL DasMahapatra, P Meigs, JB Schork, NJ Magnussen, CG Chen, W Raitakari, OT Pencina, MJ Jamal, SM Berenson, GS Goodman, E AF Vassy, Jason L. DasMahapatra, Pronabesh Meigs, James B. Schork, Nicholas J. Magnussen, Costan G. Chen, Wei Raitakari, Olli T. Pencina, Michael J. Jamal, Seema M. Berenson, Gerald S. Goodman, Elizabeth TI Genotype Prediction of Adult Type 2 Diabetes From Adolescence in a Multiracial Population SO PEDIATRICS LA English DT Article DE genetic predisposition to disease; diabetes mellitus; type 2; adolescent medicine ID GENOME-WIDE ASSOCIATION; IMPAIRED GLUCOSE-TOLERANCE; SCHOOL-BASED INTERVENTION; LARGE-SCALE ASSOCIATION; RISK-FACTORS; CHILDHOOD PREDICTORS; SUSCEPTIBILITY LOCI; INSULIN-RESISTANCE; EUROPEAN-SOCIETY; COMPLEX DISEASES AB BACKGROUND: Understanding the risk for type 2 diabetes (T2D) early in the life course is important for prevention. Whether genetic information improves prediction models for diabetes from adolescence into adulthood is unknown. METHODS: With the use of data from 1030 participants in the Bogalusa Heart Study aged 12 to 18 followed into middle adulthood, we built Cox models for incident T2D with risk factors assessed in adolescence (demographics, family history, physical examination, and routine biomarkers). Models with and without a 38 single-nucleotide polymorphism diabetes genotype score were compared by C statistics and continuous net reclassification improvement indices. RESULTS: Participant mean (+/- SD) age at baseline was 14.4 +/- 1.6 years, and 32% were black. Ninety (8.7%) participants developed T2D over a mean 26.9 +/- 5.0 years of follow-up. Genotype score significantly predicted T2D in all models. Hazard ratios ranged from 1.09 per risk allele (95% confidence interval 1.03-1.15) in the basic demographic model to 1.06 (95% confidence interval 1.00-1.13) in the full model. The addition of genotype score did not improve the discrimination of the full clinical model (C statistic 0.756 without and 0.760 with genotype score). In the full model, genotype score had weak improvement in reclassification (net reclassification improvement index 0.261). CONCLUSIONS: Although a genotype score assessed among white and black adolescents is significantly associated with T2D in adulthood, it does not improve prediction over clinical risk factors. Genetic screening for T2D in its current state is not a useful addition to adolescents' clinical care. Pediatrics 2012;130:e1235-e1242 C1 [Goodman, Elizabeth] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, Boston, MA 02114 USA. [Vassy, Jason L.; Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Vassy, Jason L.; Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Goodman, Elizabeth] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [DasMahapatra, Pronabesh; Chen, Wei; Berenson, Gerald S.] Tulane Univ, Sch Med, Ctr Cardiovasc Hlth, New Orleans, LA 70112 USA. [Schork, Nicholas J.] Scripps Res Inst, La Jolla, CA 92037 USA. [Schork, Nicholas J.] Scripps Translat Sci Inst, La Jolla, CA USA. [Magnussen, Costan G.] Menzies Res Inst, Hobart, Tas, Australia. [Magnussen, Costan G.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli T.] Turku Univ Hosp, FIN-20520 Turku, Finland. [Pencina, Michael J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Jamal, Seema M.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA. RP Goodman, E (reprint author), Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Res & Policy, 100 Cambridge St,15th Floor,C100, Boston, MA 02114 USA. EM egoodman3@partners.org RI Magnussen, Costan/J-7177-2014 OI Magnussen, Costan/0000-0002-6238-5730 FU NIH National Research Service Award from the Health Resources and Services Administration [T32 HP12706]; NIH Loan Repayment Program (NIDDK); NIH [K24 DK080140, R01 DK078616, DK046200]; NIH/NCRR [UL1 RR025774]; NHMRC Early Career Fellowship (Public Health Fellowship) [APP1037559]; National Institute of Child Health and Human Development [HD-061437, HD-062783]; National Institute on Aging [AG-16592] FX Dr Vassy is supported by NIH National Research Service Award grant T32 HP12706 from the Health Resources and Services Administration and the NIH Loan Repayment Program (NIDDK); Dr Meigs is supported by NIH grants K24 DK080140 and R01 DK078616; Dr Schork is funded in part by NIH/NCRR grant UL1 RR025774; Dr Magnussen holds an NHMRC Early Career Fellowship (Public Health Fellowship, APP1037559); Dr Goodman is supported by NIH grant DK046200; Drs DasMahapatra, Chen, and Berenson are supported by grants HD-061437 and HD-062783 from the National Institute of Child Health and Human Development and AG-16592 from the National Institute on Aging. Funded by the National Institutes of Health (NIH). NR 60 TC 19 Z9 19 U1 1 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2012 VL 130 IS 5 BP E1235 EP E1242 DI 10.1542/peds.2012-1132 PG 8 WC Pediatrics SC Pediatrics GA 029OT UT WOS:000310505900023 PM 23071215 ER PT J AU Gordon, CR Susarla, SM Yaremchuk, MJ AF Gordon, Chad R. Susarla, Srinivas M. Yaremchuk, Michael J. TI Quantitative Assessment of Medial Orbit Fracture Repair Using Computer-Designed Anatomical Plates SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID TITANIUM MESH PLATES; WALL FRACTURES; BLOWOUT FRACTURES; TRANSCARUNCULAR APPROACH; VOLUME MEASUREMENT; POSTTRAUMATIC ENOPHTHALMOS; RECONSTRUCTION; FLOOR; TRANSCONJUNCTIVAL; TOMOGRAPHY AB Background: The purpose of this study was to objectively assess the accuracy of orbital reconstruction in patients with medial wall fractures following placement of computer-designed, prebent anatomical mesh plates by means of a transconjunctival-retrocaruncular approach. Methods: This was a retrospective, cohort study of consecutive subjects with facial trauma who underwent reconstruction of medial wall/orbital floor defects over a 12-month period at a level I trauma center. All subjects had preoperative and postoperative computed tomographic scans with 1.25-mm slices formatted in the axial, coronal, and sagittal planes with aminimum of 3months' follow-up. Preoperative and postoperative orbital volumes were computed using integrated analysis over the orbital slices. The volumes were compared using nonparametric paired samples comparisons (Wilcoxon signed ranks test). For all analyses, p <= 0.05 was considered significant. Results: Fifteen subjects underwent repair of 17 medial wall fractures. The mean patient age was 37 +/- 16 years (range, 18 to 59 years); one subject was female. Motor vehicle-related incidents and assaults were the most common mechanisms of injury. The average postoperative volume for the fractured sides was 22.2 +/- 2.1 cm(3) (range, 19.9 to 26.9 cm(3)) and was statistically significantly lower than the preoperative volume on the fractured side (24.18 +/- 2.57 cm(3); p < 0.001). One patient (6.7 percent) experienced a postoperative complication requiring reoperation. Conclusion: Computer-designed, prebent anatomical mesh plates placed using a transconjunctival-retrocaruncular approach for reconstruction of medial wall fractures with orbital floor components reliably results in restoration of contour and volume, with a low complication rate. (Plast. Reconstr. Surg. 130: 698e, 2012.) C1 [Yaremchuk, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Plast & Reconstruct Surg, Boston, MA 02116 USA. Johns Hopkins Univ, Sch Med, Dept Plast & Reconstruct Surg, Johns Hopkins Hosp, Baltimore, MD USA. Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Dent Med, Boston, MA 02116 USA. RP Yaremchuk, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Plast & Reconstruct Surg, WACC 435, Boston, MA 02116 USA. EM dr.y@dryaremchuk.com OI Susarla, Srinivas/0000-0003-0155-8260 NR 35 TC 13 Z9 13 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 2012 VL 130 IS 5 BP 698E EP 705E DI 10.1097/PRS.0b013e3182686358 PG 8 WC Surgery SC Surgery GA 030LL UT WOS:000310572100007 PM 23096623 ER PT J AU Jones, NF Jupiter, JB Lalonde, DH AF Jones, Neil F. Jupiter, Jesse B. Lalonde, Donald H. TI Common Fractures and Dislocations of the Hand SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PROXIMAL INTERPHALANGEAL JOINT; ULNAR COLLATERAL LIGAMENT; METACARPAL NECK FRACTURES; VOLAR PLATE ARTHROPLASTY; KIRSCHNER WIRE FIXATION; PHALANGEAL FRACTURES; INTERNAL-FIXATION; SCREW FIXATION; LONG-TERM; EXTERNAL FIXATION AB Learning Objectives: After reading this article, the participant should be able to: 1. Describe the concept of early protected movement with Kirschner-wired finger fractures to the hand therapist. 2. Choose the most appropriate method of fracture fixation to achieve the goal of a full range of motion. 3. Describe the methods of treatment available for the most common fractures and dislocations of the hand. Background: The main goal of treatment of hand and finger fractures and dislocations is to attain a full range of wrist and nonscissoring finger motion after the treatment is accomplished. This CME article consists of literature review, illustrations, movies, and an online CME examination to bring the participant recent available information on the topic. Methods: The authors reviewed literature regarding the most current treatment strategies for common hand and finger fractures and dislocations. Films were created to illustrate operative and rehabilitation methods used to treat these problems. A series of multiple-choice questions, answers, discussions, and references were written and are provided online so that the participant can receive the full benefit of this review. Results: Many treatment options are available, from buddy and Coban taping to closed reduction with immobilization; percutaneous pins or screws; and open reduction with pins, screws, or plates. Knowledge of all available options is important because all can be used to achieve the goal of treatment in the shortest time possible. The commonly used methods of treatment are reviewed and illustrated. Conclusions: Management of common hand and finger fractures and dislocations includes the need to focus on achieving a full range of motion after treatment. A balance of fracture reduction with minimal dissection and early protected movement will achieve the goal. (Plast. Reconstr. Surg. 130: 722e, 2012.) C1 [Jones, Neil F.] Univ Calif Irvine, Med Ctr, Dept Orthoped Surg, Orange, CA 92868 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. Dalhousie Univ, St John, NB, Canada. RP Jones, NF (reprint author), Univ Calif Irvine, Med Ctr, Dept Orthoped Surg, 101 City Dr S,Pavil 3, Orange, CA 92868 USA. EM nfjones@uci.edu NR 95 TC 13 Z9 13 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 2012 VL 130 IS 5 BP 722E EP 736E DI 10.1097/PRS.0b013e318267d67a PG 15 WC Surgery SC Surgery GA 030LL UT WOS:000310572100011 PM 23096627 ER PT J AU Hoe, M Nakagami, E Green, MF Brekke, JS AF Hoe, M. Nakagami, E. Green, M. F. Brekke, J. S. TI The causal relationships between neurocognition, social cognition and functional outcome over time in schizophrenia: a latent difference score approach SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Causal relationship; neurocognition; psychosocial rehabilitation; schizophrenia; social cognition ID FACIAL AFFECT RECOGNITION; PSYCHIATRIC RATING-SCALE; NEGATIVE SYMPTOMS; PSYCHOSOCIAL REHABILITATION; EMOTION PERCEPTION; NEURAL BASIS; DEFICITS; INDIVIDUALS; PERFORMANCE; EXPERIENCE AB Background. Social cognition has been identified as a significant construct for schizophrenia research with relevance to diagnosis, assessment, treatment and functional outcome. However, social cognition has not been clearly understood in terms of its relationships with neurocognition and functional outcomes. The present study sought to examine the empirical independence of social cognition and neurocognition; to investigate the possible causal structure among social cognition, neurocognition and psychosocial functioning. Method. The sample consists of 130 individuals diagnosed with schizophrenia. All participants were recruited as they were admitted to four community-based psychosocial rehabilitation programs. Social cognition, neurocognition and psychosocial functioning were measured at baseline and 12 months. The empirical independence of social cognition and neurocognition was tested using confirmatory factor analysis (CFA) and the possible causal structure among social cognition, neurocognition and psychosocial functioning was investigated using latent difference score (LDS) analysis. Results. A two-factor model of social cognition and neurocognition fit the data very well, indicating the empirical independence of social cognition, whereas the longitudinal CFA results show that the empirical independence of neurocognition and social cognition is maintained over time. The results of the LDS analysis support a causal model that indicates that neurocognition underlies and is causally primary to social cognition, and that neurocognition and social cognition are causally primary to functional outcome. Conclusions. Social cognition and neurocognition could have independent and distinct upward causal effects on functional outcome. It is also suggested that the approaches for remediation of neurocognition and social cognition might need to be distinct. C1 [Hoe, M.] Keimyung Univ, Coll Social Sci, Dept Social Welf, Taegu 704701, South Korea. [Nakagami, E.; Brekke, J. S.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [Green, M. F.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Hoe, M (reprint author), Keimyung Univ, Coll Social Sci, Dept Social Welf, 2800 Dalgubeoldearo, Taegu 704701, South Korea. EM maanse@kmu.ac.kr FU NCATS NIH HHS [UL1 TR000130] NR 81 TC 27 Z9 28 U1 1 U2 23 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2012 VL 42 IS 11 BP 2287 EP 2299 DI 10.1017/S0033291712000578 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 031HI UT WOS:000310629600005 PM 22475159 ER PT J AU Jin, J Park, M Rengarajan, A Zhang, Q Limburg, S Joshi, SK Patel, S Kim, HT Kuo, AC AF Jin, Jenny Park, Michelle Rengarajan, Arvind Zhang, Qia Limburg, Sonja Joshi, Sunil K. Patel, Shyam Kim, Hubert T. Kuo, Alfred C. TI Functional motor recovery after peripheral nerve repair with an aligned nanofiber tubular conduit in a rat model SO REGENERATIVE MEDICINE LA English DT Article DE longitudinal alignment; nerve conduit; peripheral nerve repair ID CONTROLLED-RELEASE; GUIDANCE CHANNELS; SKELETAL-MUSCLE; REGENERATION; INJURIES; MICROSPHERES; OUTCOMES; GUIDES; ULNAR AB Aim: Current synthetic tubular conduits are inferior to nerve autograft for the repair of segmental peripheral nerve injuries. We examined motor outcomes with the use of longitudinally aligned poly (L-lactide-co-caprolactone) nanofiber conduits for repair of nerve gap injury in a rat model. Methods: Ten-millimeter segments of sciatic nerve were resected in 44 Lewis rats. The gaps were either left unrepaired (n = 6), repaired with nerve autograft (n = 19), or repaired with conduit (n = 19). After 12 weeks, nerve conduction latency, compound muscle action potential amplitude, muscle force and muscle mass were measured. The numbers of axons and axon diameters both within the grafts and distally were determined. Results: After 12 weeks, gastrocnemius isometric tetanic force and muscle mass for the conduit group reached 85 and 82% of autograft values, respectively. Nerve conduction and compound muscle action potential were not significantly different between these two groups, although the latter approached significance. There was no recovery in the unrepaired group. Conclusion: Muscle recovery for the animals treated with this aligned nanofiber conduit approached that of autograft, suggesting the importance of internal conduit structure for nerve repair. C1 [Jin, Jenny; Park, Michelle; Rengarajan, Arvind; Zhang, Qia; Limburg, Sonja; Joshi, Sunil K.; Kim, Hubert T.; Kuo, Alfred C.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Jin, Jenny; Park, Michelle; Rengarajan, Arvind; Zhang, Qia; Limburg, Sonja; Joshi, Sunil K.; Kim, Hubert T.; Kuo, Alfred C.] Univ Calif San Francisco, Dept Orthoped Surg, San Francisco, CA 94143 USA. [Patel, Shyam] NanoNerve Inc, Berkeley, CA USA. RP Kuo, AC (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 112, San Francisco, CA 94121 USA. EM kuoac@orthosurg.ucsf.edu NR 36 TC 8 Z9 9 U1 1 U2 31 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0751 J9 REGEN MED JI Regen. Med. PD NOV PY 2012 VL 7 IS 6 BP 799 EP 806 DI 10.2217/RME.12.87 PG 8 WC Cell & Tissue Engineering; Engineering, Biomedical SC Cell Biology; Engineering GA 031QC UT WOS:000310656000015 PM 23164080 ER PT J AU Gurubhagavatula, I AF Gurubhagavatula, Indira TI Does the Rubber Meet the Road? Addressing Sleep Apnea in Commercial Truck Drivers SO SLEEP LA English DT Editorial Material ID MOTOR-VEHICLE CRASH; RISK; METAANALYSIS C1 [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Div Sleep Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm Crit Care & Sleep Sect, Philadelphia, PA USA. [Gurubhagavatula, Indira] Univ Penn, Med Ctr, Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. RP Gurubhagavatula, I (reprint author), Univ Penn, Med Ctr, Div Sleep Med, Perelman Sch Med, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM gurubhag@mail.med.upenn.edu FU NIOSH CDC HHS [R01 OH009149, R01-OH009149] NR 26 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2012 VL 35 IS 11 BP 1443 EP 1444 DI 10.5665/sleep.2180 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 030NU UT WOS:000310578200002 PM 23115390 ER PT J AU Morales, CR Hurley, S Wick, LC Staley, B Pack, FM Gooneratne, NS Maislin, G Pack, A Gurubhagavatula, I AF Morales, Christian R. Hurley, Sharon Wick, Lindsay C. Staley, Bethany Pack, Frances M. Gooneratne, Nalaka S. Maislin, Greg Pack, Allan Gurubhagavatula, Indira TI In-Home, Self-Assembled Sleep Studies Are Useful in Diagnosing Sleep Apnea in the Elderly SO SLEEP LA English DT Article DE Aged adults; obstructive sleep apnea; portable sleep studies; screening ID OLDER-ADULTS; DAYTIME SLEEPINESS; APNOEA/HYPOPNOEA SYNDROME; HEART HEALTH; POLYSOMNOGRAPHY; RISK; MEN; AUTOSET(TM); POPULATION; DISORDERS AB Objectives: Obstructive sleep apnea (OSA) is common and treatable among the elderly. Yet, few older adults seek evaluation for OSA at sleep disorders centers. The authors assessed the feasibility of a two-stage screening procedure for obstructive sleep apnea syndrome (OSAS) in a community-based sample of older adults. Design: Prospective cohort study. Setting: Participants' domicile (in-home) and academic sleep research center. Participants: There were 452 Medicare recipients residing in the greater Philadelphia metropolitan area with the complaint of daytime sleepiness. Interventions: None. Measurements and Results: All participants underwent in-home unattended sleep studies that recorded airflow, and standard in-laboratory polysomnography. Additional measures included symptoms of sleep apnea, body mass index, neck circumference, age, and sex. When comparing diagnostic approaches, the best-performing single-stage model was one that combined apnea symptoms with age and neck circumference. This model had an area under the receiver operating characteristic curve (AUC) of 0.774 and negative posttest probability of 1.2%. The best-performing two-stage model combined symptoms, neck circumference, age, and sex in the first stage, followed by an unattended portable study with a corresponding AUC of 0.85 and negative posttest probability of 0.5%. Conclusions: Unattended, self-assembled, in-home sleep studies recording airflow and respiratory effort are most useful if applied in tandem with clinical data, including a carefully obtained sleep history. This two-stage model is accurate in identifying severe OSAS in older adults and represents a practical diagnostic approach for older adults. Incorporating clinical data was vital and increased accuracy well above that of unattended studies of airflow and effort alone. C1 [Morales, Christian R.; Hurley, Sharon; Wick, Lindsay C.; Staley, Bethany; Pack, Frances M.; Gooneratne, Nalaka S.; Maislin, Greg; Pack, Allan; Gurubhagavatula, Indira] Univ Penn, Ctr Sleep & Circadian Neurobiol, Sch Med, Philadelphia, PA 19104 USA. [Gooneratne, Nalaka S.; Pack, Allan; Gurubhagavatula, Indira] Univ Penn, Med Ctr, Div Sleep Med, Dept Med, Philadelphia, PA 19104 USA. [Gooneratne, Nalaka S.] Univ Penn, Div Geriatr Med, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Gurubhagavatula, Indira] Philadelphia VA Med Ctr, Pulm & Crit Care & Sleep Sect, Philadelphia, PA USA. RP Gurubhagavatula, I (reprint author), Univ Penn, Ctr Sleep & Circadian Neurobiol, Sch Med, 3624 Market St,Suite 205, Philadelphia, PA 19104 USA. EM gu-rubhag@mail.med.upenn.edu FU NIH [T32 HL07713, R01-HL060756, K23 RR16068, R01-OH009149]; Takeda Pharmaceuticals; Respironics; Phillips/Respironics Foundation FX This work was performed at the University of Pennsylvania and supported by NIH T32 HL07713, R01-HL060756, K23 RR16068, and R01-OH009149. ResMed, Inc. provided an unrestricted loan for use of portable diagnostic sleep study equipment (AutoSet (TM)) and had no role in protocol development, data collection, storage, analysis, or manuscript preparation.; This was not an industry supported study; however, ResMed, Inc. provided an unrestricted loan for use of portable diagnostic sleep study equipment (AutoSet (TM)) and had no role in protocol development, data collection, storage, analysis, or manuscript preparation. Dr. Gooneratne has received research grants from Takeda Pharmaceuticals and Respironics. Dr. Gurubhagavatula has been loaned equipment for research purposes from Embla, Inc. Dr. Maislin is the principal bio-statistician of Biomedical Statistical Consulting (BSC). Dr. Pack has been endowed with funds provided by the Phillips/Respironics Foundation. The other authors have indicated no financial conflicts of interest. NR 44 TC 14 Z9 14 U1 0 U2 3 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2012 VL 35 IS 11 BP 1491 EP 1501 DI 10.5665/sleep.2196 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 030NU UT WOS:000310578200010 PM 23115398 ER PT J AU Eisner, BH Thavaseelan, S Sheth, S Haleblian, G Pareek, G AF Eisner, Brian H. Thavaseelan, Simone Sheth, Sonali Haleblian, George Pareek, Gyan TI Relationship Between Serum Vitamin D and 24-Hour Urine Calcium in Patients With Nephrolithiasis SO UROLOGY LA English DT Article ID D DEFICIENCY; POSTMENOPAUSAL WOMEN; KIDNEY-STONES; RISK; SUPPLEMENTATION; PREVALENCE AB OBJECTIVE To examine the relationship between serum 25-OH vitamin D and 24-hour urine calcium in patients with nephrolithiasis. METHODS A retrospective review was performed. Patients evaluated in 2 metabolic stone clinics were included for analysis. Multivariate linear regression models were adjusted for known risk factors for stone disease (age, gender, body mass index, hypertension, diabetes mellitus, gout, relevant medications, and 24-hour urine composition). RESULTS One-hundred sixty-nine patients were included in the study. Female to male ratio was 69:100, mean age was 50.9 years (SD 13.7), and mean body mass index was 27.4 (SD 6.4). Vitamin D deficiency (25-OH vitamin D <20 ng/mL) was present in 18.9% of patients, vitamin D insufficiency (>20, <30 ng/mL) was present in 34.9% of patients, and vitamin D was within normal limits (>= 30 ng/mL) in 46.1% of patients. On age-adjusted and multivariate linear regression, serum 25-OH vitamin D was not related to 24-hour urine calcium (age adjusted beta = -0.31 m 95% CI -1.9 to 1.3; multivariate adjusted beta = 0.08, 95% CI -1.3 to 1.5). CONCLUSION Although 25-OH vitamin D is involved in the body's calcium homeostasis, our study does not show a relationship between serum vitamin D level and 24-hour urine calcium excretion in stone-formers. This information may have implications regarding the safety of vitamin D repletion in patients with nephrolithiasis. UROLOGY 80: 1007-1010, 2012. (C) 2012 Elsevier Inc. C1 [Eisner, Brian H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. Brown Univ, Warren Alpert Sch Med, Dept Urol, Providence, RI 02912 USA. RP Eisner, BH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org FU Boston Scientific; Olympus/ACMI; PercSys; Ravine Group FX Brian Eisner is a consultant for Boston Scientific, Olympus/ACMI, PercSys, and owner of the Ravine Group. NR 19 TC 13 Z9 13 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2012 VL 80 IS 5 BP 1007 EP 1010 DI 10.1016/j.urology.2012.04.041 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 030JF UT WOS:000310566300024 PM 22698470 ER PT J AU Byun, H Hillman, TR Higgins, JM Diez-Silva, M Peng, ZL Dao, M Dasari, RR Suresh, S Park, Y AF Byun, HeeSu Hillman, Timothy R. Higgins, John M. Diez-Silva, Monica Peng, Zhangli Dao, Ming Dasari, Ramachandra R. Suresh, Subra Park, YongKeun TI Optical measurement of biomechanical properties of individual erythrocytes from a sickle cell patient SO ACTA BIOMATERIALIA LA English DT Article DE Sickle cell disease; Red blood cell; Cell biomechanics; Cell membrane; Optical measurement ID RED-BLOOD-CELLS; DIFFRACTION PHASE; MEMBRANE SKELETON; LIPID-BILAYERS; DISEASE; DYNAMICS; HEMOGLOBIN; ELASTICITY; MICROSCOPY; ANEMIA AB Sickle cell disease (SCD) is characterized by the abnormal deformation of red blood cells (RBCs) in the deoxygenated condition, as their elongated shape leads to compromised circulation. The pathophysiology of SCD is influenced by both the biomechanical properties of RBCs and their hemodynamic properties in the microvasculature. A major challenge in the study of SCD involves accurate characterization of the biomechanical properties of individual RBCs with minimum sample perturbation. Here we report the biomechanical properties of individual RBCs from a SCD patient using a non-invasive laser interferometric technique. We optically measure the dynamic membrane fluctuations of RBCs. The measurements are analyzed with a previously validated membrane model to retrieve key mechanical properties of the cells: bending modulus; shear modulus; area expansion modulus; and cytoplasmic viscosity. We find that high cytoplasmic viscosity at ambient oxygen concentration is principally responsible for the significantly decreased dynamic membrane fluctuations in RBCs with SCD, and that the mechanical properties of the membrane cortex of irreversibly sickled cells (ISCs) are different from those of the other types of RBCs in SCD. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Diez-Silva, Monica; Peng, Zhangli; Dao, Ming; Suresh, Subra] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Byun, HeeSu; Park, YongKeun] Korea Adv Inst Sci & Technol, Dept Phys, Taejon 305701, South Korea. [Hillman, Timothy R.; Dasari, Ramachandra R.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Higgins, John M.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Higgins, John M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Higgins, John M.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02114 USA. RP Dao, M (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. EM mingdao@mit.edu; yk.park@kasit.ac.kr RI Park, YongKeun/B-9017-2009; Dao, Ming/B-1602-2008; Peng, Zhangli/N-7284-2016 FU National Institutes of Health at MIT [9P41-EB015871-26A1, R01HL094270, DK083242]; KAIST, KAIST Institute for Optical Science and Technology; Korean Ministry of Education, Science and Technology (MEST) [2009-0087691]; National Research Foundation [NRF-2012R1A1A1009082]; Infectious Diseases Interdisciplinary Research Group; Singapore-MIT Alliance for Research and Technology (SMART) Center; TJ ChungAm Foundation FX The authors wish to acknowledge Prof. Mahn Won Kim (KAIST), Prof. Philip A. Pincus (University of California, Santa Barbara), and Prof. George Karniadakis and Dr Xuejin Li (Brown University) for helpful discussions. This work was supported by National Institutes of Health (under grants 9P41-EB015871-26A1, R01HL094270 and DK083242) at MIT, and by KAIST, KAIST Institute for Optical Science and Technology, the Korean Ministry of Education, Science and Technology (MEST) grant No. 2009-0087691 (BRL), and National Research Foundation (NRF-2012R1A1A1009082). Partial support from the Infectious Diseases Interdisciplinary Research Group funded by the Singapore-MIT Alliance for Research and Technology (SMART) Center is also acknowledged. YKP acknowledges support from TJ ChungAm Foundation. NR 60 TC 38 Z9 38 U1 4 U2 34 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 J9 ACTA BIOMATER JI Acta Biomater. PD NOV PY 2012 VL 8 IS 11 BP 4130 EP 4138 DI 10.1016/j.actbio.2012.07.011 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 028BV UT WOS:000310398700026 PM 22820310 ER PT J AU McNicholas, LF Holbrook, AM O'Grady, KE Jones, HE Coyle, MG Martin, PR Heil, SH Stine, SM Kaltenbach, K AF McNicholas, Laura F. Holbrook, Amber M. O'Grady, Kevin E. Jones, Hendree E. Coyle, Mara G. Martin, Peter R. Heil, Sarah H. Stine, Susan M. Kaltenbach, Karol TI Effect of hepatitis C virus status on liver enzymes in opioid-dependent pregnant women maintained on opioid-agonist medication SO ADDICTION LA English DT Article DE Buprenorphine; liver transaminases; methadone; opioids; pregnancy ID NEONATAL ABSTINENCE SYNDROME; OPIATE DEPENDENCE; DOUBLE-BLIND; BUPRENORPHINE; METHADONE; ADDICTION; TRIAL; OUTCOMES; SAMPLE; ABUSE AB Aim To examine hepatic enzyme test results throughout the course of pregnancy in women maintained on methadone or buprenorphine. Design Participants were randomized to either methadone or buprenorphine maintenance. Blood chemistry tests, including liver transaminases and hepatitis C virus (HCV) status, were determined every 4 weeks and once postpartum. As part of a planned secondary analysis, generalized mixed linear models were conducted with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) as the dependent variables. Setting Six US sites and one European site that provided comprehensive treatment to pregnant opioid-dependent women. Participants A total of 175 opioid-dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. Findings ALT, AST and GGT levels decreased for all subjects across pregnancy trimesters, rising slightly postpartum. HCV-positive subjects exhibited higher transaminases at all time-points compared to HCV-negative subjects, regardless of medication (all Ps<0.05) condition. Both HCV-positive and negative buprenorphine-maintained participants exhibited lower GGT levels than those who were methadone-maintained (P<0.05). Conclusions Neither methadone nor buprenorphine appear to have adverse hepatic effects in the treatment of pregnant opioid-dependent women. C1 [McNicholas, Laura F.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [McNicholas, Laura F.] Philadelphia VA Med Ctr, Dept Vet Affairs, Philadelphia, PA USA. [Holbrook, Amber M.; Kaltenbach, Karol] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. [O'Grady, Kevin E.] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. [Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Jones, Hendree E.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. [Jones, Hendree E.] RTI Int, Res Triangle Pk, NC USA. [Coyle, Mara G.] Brown Univ, Dept Pediat, Warren Alpert Med Sch, Providence, RI 02912 USA. [Martin, Peter R.] Vanderbilt Univ, Sch Med, Dept Psychiat, Vanderbilt Addict Ctr, Nashville, TN 37212 USA. [Martin, Peter R.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Vanderbilt Addict Ctr, Nashville, TN 37212 USA. [Heil, Sarah H.] Univ Vermont, Dept Psychiat, Burlington, VT USA. [Heil, Sarah H.] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Stine, Susan M.] Wayne State Univ, Dept Psychiat & Behav Neurosci, Detroit, MI USA. [Kaltenbach, Karol] Thomas Jefferson Univ, Jefferson Med Coll, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. RP Kaltenbach, K (reprint author), 1233 Locust St,401, Philadelphia, PA 19107 USA. EM Karol.Kaltenbach@jefferson.edu RI Martin, Peter/A-7738-2008; OI Stine, Susan/0000-0001-5426-4448 FU National Institute on Drug Abuse (NIDA); National Institute on Drug Abuse (NIDA), Brown University [R01 DA 015778]; National Institute on Drug Abuse (NIDA), Johns Hopkins University [R01 DA 015764]; National Institute on Drug Abuse (NIDA), Medical University of Vienna [R01 DA 018417]; National Institute on Drug Abuse (NIDA), Thomas Jefferson University [R01 DA 015738]; National Institute on Drug Abuse (NIDA), University of Toronto [R01 DA 015741]; National Institute on Drug Abuse (NIDA), University of Vermont [R01 DA 018410, M01 RR 109]; National Institute on Drug Abuse (NIDA), Vanderbilt University [R01 DA 017513, M01 RR 00095]; National Institute on Drug Abuse (NIDA), Wayne State University [R01 DA 15832]; Reckitt Benckiser; Schering Plough; Schering Canada; Government of Ontario FX All MOTHER grants are from the National Institute on Drug Abuse (NIDA) unless noted otherwise: Brown University, R01 DA 015778; Johns Hopkins University, R01 DA 015764; Medical University of Vienna, R01 DA 018417; Thomas Jefferson University, R01 DA 015738; University of Toronto, R01 DA 015741; University of Vermont, R01 DA 018410 and M01 RR 109; Vanderbilt University, R01 DA 017513 and M01 RR 00095, and Wayne State University, R01 DA 15832.; G. F. discloses that she has received financial support and honoraria for presentations from Reckitt Benckiser, as well as financial support and honoraria for presentations from Schering Plough.; P. S. discloses that he has received an unrestricted educational grant from Schering Canada to provide a single training program on buprenorphine treatment in 2000. His hospital receives funds from the Government of Ontario to develop and provide a training program of which he is the course director for all Ontario physicians who wish to treat opioid dependence including in pregnant women. However, the buprenorphine mono product is not available in Canada. NR 26 TC 8 Z9 8 U1 3 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0965-2140 J9 ADDICTION JI Addiction PD NOV PY 2012 VL 107 SU 1 SI SI BP 91 EP 97 DI 10.1111/j.1360-0443.2012.04043.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 029EN UT WOS:000310477700010 PM 23106931 ER PT J AU Alhassoon, OM Sorg, SF Taylor, MJ Stephan, RA Schweinsburg, BC Stricker, NH Gongvatana, A Grant, I AF Alhassoon, Omar M. Sorg, Scott F. Taylor, Michael J. Stephan, Rick A. Schweinsburg, Brian C. Stricker, Nikki H. Gongvatana, Assawin Grant, Igor TI Callosal White Matter Microstructural Recovery in Abstinent Alcoholics: A Longitudinal Diffusion Tensor Imaging Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Diffusion Tensor Imaging; White Matter; Alcohol Dependence; Abstinence; Tract-Based Spatial Statistics ID CORPUS-CALLOSUM; MAGNETIC-RESONANCE; BRAIN-DAMAGE; CEREBRAL-CORTEX; IN-VIVO; TRACTOGRAPHY; CONSUMPTION; INTEGRITY; MEN; AGE AB Background Previous neuroimaging studies of recently detoxified alcohol-dependent patients (RDA) have found significant loss of white matter integrity associated with the shrinkage of the frontal lobes and thinning of the corpus callosum, especially the genu. The current study hypothesized that, in addition to exhibiting the most microstructural white matter disruption in RDA, the genu will also evidence the most recovery after abstinence. This microstructural recovery will be associated with improvements in executive functioning measures. Methods Fifteen RDA were examined approximately 2 weeks after abstinence and again after 1 year of abstinence and compared to 15 age- and education-matched nonalcoholic controls using diffusion tensor imaging (DTI). The effects of group, time, and their interactions on fractional anisotropy, radial diffusivity, and axial diffusivity were evaluated with repeated measures MANOVA; in addition, 2 x 2 ANOVA was used to test changes in measures of executive functioning in the 2 groups. Results At 2 weeks of abstinence, DTI of RDA showed significantly lower fractional anisotropy and greater radial diffusivity compared to controls in the genu and body of the corpus callosum. Reexamination after 1 year showed significant time by group interaction with fractional anisotropy increasing and radial diffusivity decreasing in RDA but not controls in these 2 regions. A smaller relapsed group did not show improvements between the 2 time points. Abstinent RDA also showed improvement on Digit Span Backward, a measure of working memory, but did not benefit from practice effects on the Halstead Category Test compared to controls. Conclusions The results suggest susceptibility of the genu and body of the corpus callosum to the effects of alcohol, and the potential for recovery of both these regions after abstinence, perhaps via mechanisms involving myelin reconstitution. C1 [Alhassoon, Omar M.; Sorg, Scott F.; Taylor, Michael J.; Grant, Igor] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Alhassoon, Omar M.; Stephan, Rick A.] Calif Sch Profess Psychol, Dept Psychol, San Diego, CA 92121 USA. [Sorg, Scott F.; Taylor, Michael J.; Grant, Igor] VA San Diego Healthcare Syst, Dept Psychiat, La Jolla, CA USA. [Sorg, Scott F.; Taylor, Michael J.; Grant, Igor] SDSU UCSD Joint Doctoral Program Clin Psychol, Dept Psychol, San Diego, CA USA. [Schweinsburg, Brian C.] Yale Univ, Dept Psychiat, West Haven, CT USA. [Stricker, Nikki H.] VA Boston Healthcare Syst, Dept Psychiat, Boston, MA USA. [Gongvatana, Assawin] Brown Univ, Dept Psychiat, Providence, RI 02912 USA. RP Grant, I (reprint author), Univ Calif San Diego, Dept Psychiat 0680, Sch Med, La Jolla, CA 92093 USA. EM igrant@ucsd.edu OI Gongvatana, Assawin/0000-0001-6102-6384 FU eterans Affairs Medical Research Service FX This project was made possible by a grant from the Veterans Affairs Medical Research Service awarded to IG. We gratefully acknowledge June Allen for her invaluable assistance throughout the course of this project. NR 54 TC 15 Z9 18 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2012 VL 36 IS 11 BP 1922 EP 1931 DI 10.1111/j.1530-0277.2012.01808.x PG 10 WC Substance Abuse SC Substance Abuse GA 029DL UT WOS:000310474900011 PM 22551067 ER PT J AU Slatore, CG Hansen, L Ganzini, L Press, N Osborne, ML Chesnutt, MS Mularski, RA AF Slatore, Christopher G. Hansen, Lissi Ganzini, Linda Press, Nancy Osborne, Molly L. Chesnutt, Mark S. Mularski, Richard A. TI COMMUNICATION BY NURSES IN THE INTENSIVE CARE UNIT: QUALITATIVE ANALYSIS OF DOMAINS OF PATIENT-CENTERED CARE SO AMERICAN JOURNAL OF CRITICAL CARE LA English DT Article ID OF-LIFE CARE; PALLIATIVE CARE; IMPROVE COMMUNICATION; FAMILY CONFERENCE; CRITICAL ILLNESS; DECISION-MAKING; PHYSICIANS; PERCEPTIONS; ICU; OPPORTUNITIES AB Background High-quality communication is a key determinant and facilitator of patient-centered care. Nurses engage in most of the communication with patients and patients' families in the intensive care unit. Objective To perform a qualitative analysis of nurses' communications. Methods Ethnographic observations of 315 hours of interactions and 53 semistructured interviews with 33 nurses were conducted in a 26-bed cardiac-medical intensive care unit in an academic hospital and a 26-bed general intensive care unit in a Veterans Affairs hospital in Portland, Oregon. Communication interactions were categorized into 5 domains of patient-centered care. Interviews were analyzed to identify major themes in nurses' roles and preferences for communicating with patients and patients' families within the domains. Results Most communication occurred in the domains of biopsychosocial information exchange, patient as person, and clinician as person. Nurses endorsed the importance of the domains of shared power and responsibility and therapeutic alliance but had relatively few communication interactions in these areas. Communication behaviors were strongly influenced by the nurses' roles as translators of information between physicians and patients and the patients' families and what the nurses were and were not willing to communicate to patients and patients' families. Conclusions Critical care, including communication, is a collaborative effort. Understanding how nurses engage in patient-centered communication in the intensive care unit can guide future interventions to improve patient-centered care. (American Journal of Critical Care. 2012;21:410-418) C1 [Slatore, Christopher G.; Osborne, Molly L.; Chesnutt, Mark S.] Portland VA Med Ctr, Sect Pulm & Crit Care Med, Portland, OR USA. [Slatore, Christopher G.; Osborne, Molly L.; Chesnutt, Mark S.; Mularski, Richard A.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Dept Med, Portland, OR 97201 USA. [Hansen, Lissi; Press, Nancy] Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97201 USA. [Press, Nancy] Oregon Hlth & Sci Univ, Sch Med, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. [Chesnutt, Mark S.] Portland VA Med Ctr, Patient Care Serv Div, Portland, OR USA. [Mularski, Richard A.] Kaiser Permanente NW, Ctr Hlth Res, Pulm & Crit Care Med, Portland, OR USA. RP Slatore, CG (reprint author), 3710 SW US Vet Hosp Rd,R&D 66, Portland, OR 97239 USA. EM christopher.slatore@va.gov OI Slatore, Christopher/0000-0003-0958-8122 FU National Institute of Nursing Research [R21 NR009845] FX Dr Slatore is a Veterans Affairs Health Services Research and Development Career Development Awardee. This study is the result of work supported by resources from the Portland Veterans Affairs Medical Center. Neither the National Institutes of Health nor the Department of Veterans Affairs had a role in the conduct of the study; in the collection, management, analysis, or interpretation of data; or in the preparation of the manuscript. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the US government.; The study was funded by grant R21 NR009845 to Dr Hansen from the National Institute of Nursing Research. NR 51 TC 20 Z9 22 U1 1 U2 31 PU AMER ASSOC CRITICAL CARE NURSES PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1062-3264 J9 AM J CRIT CARE JI Am. J. Crit. Care PD NOV 1 PY 2012 VL 21 IS 6 BP 410 EP 418 DI 10.4037/ajcc2012124 PG 9 WC Critical Care Medicine; Nursing SC General & Internal Medicine; Nursing GA 031LO UT WOS:000310642100006 PM 23117904 ER PT J AU Simon, HB AF Simon, Harvey B. TI Medicine and the Humanities: Joining Two Cultures SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Simon, Harvey B.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Simon, Harvey B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Simon, Harvey B.] MIT, Hlth Sci Technol Fac, Cambridge, MA 02139 USA. RP Simon, HB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM hsimon@partners.org NR 2 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2012 VL 125 IS 11 BP 1144 EP 1145 DI 10.1016/j.amjmed.2012.06.006 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 028OQ UT WOS:000310432200035 PM 22939095 ER PT J AU Baicu, CF Li, JY Zhang, YH Kasiganesan, H Cooper, G Zile, MR Bradshaw, AD AF Baicu, Catalin F. Li, Jiayu Zhang, Yuhua Kasiganesan, Harinath Cooper, George Zile, Michael R. Bradshaw, Amy D. TI Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE procollagen; SPARC; osteonectin; cardiac fibroblasts; fibrosis ID CAT RIGHT VENTRICLE; CARDIAC-HYPERTROPHY; HEART-FAILURE; COLLAGEN-SYNTHESIS; GENE-EXPRESSION; CYSTEINE SPARC; PROTEIN; DEGRADATION; REGRESSION; RATS AB Baicu CF, Li J, Zhang Y, Kasiganesan H, Cooper G IV, Zile MR, Bradshaw AD. Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing. Am J Physiol Heart Circ Physiol 303: H1128-H1134, 2012. First published August 31, 2012; doi:10.1152/ajpheart.00482.2012.-Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 +/- 1.03 mg/g vs. 2-wk PAB: 11.50 +/- 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 +/- 0.25% vs. 4-wk PAB: 4.18 +/- 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function. C1 [Bradshaw, Amy D.] Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Vet Affairs Med Ctr, Ralph H Johnson Dept, Charleston, SC 29403 USA. RP Bradshaw, AD (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, Gazes Cardiac Res Inst, 114 Doughty St, Charleston, SC 29425 USA. EM bradshad@musc.edu FU Research Service of the Department of Veterans Affairs [5101CX000415-02, 5101BX000487-04, 1I01BX001385-01A1]; National Heart, Lung, and Blood Institute [PO1-HL-48788, RO1-HL-094517] FX This study was supported by the Research Service of the Department of Veterans Affairs (M. R. Zile: 5101CX000415-02 and 5101BX000487-04 and A. D. Bradshaw: 1I01BX001385-01A1) and grants from the National Heart, Lung, and Blood Institute (PO1-HL-48788 to G. Cooper and M. R. Zile; RO1-HL-094517 to A. D. Bradshaw). NR 33 TC 13 Z9 13 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2012 VL 303 IS 9 BP H1128 EP H1134 DI 10.1152/ajpheart.00482.2012 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 031OA UT WOS:000310650300005 PM 22942178 ER PT J AU Grant, JE Odlaug, BL Chamberlain, SR Keuthen, NJ Lochner, C Stein, DJ AF Grant, Jon E. Odlaug, Brian L. Chamberlain, Samuel R. Keuthen, Nancy J. Lochner, Christine Stein, Dan J. TI Skin Picking Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; PSYCHOGENIC EXCORIATION; DOUBLE-BLIND; OPEN-LABEL; COMMUNITY SAMPLE; PREVALENCE; PHENOMENOLOGY; BEHAVIOR; TRICHOTILLOMANIA; INDIVIDUALS AB Although skin picking has been documented in the medical literature since the 19th century, only now is it receiving serious consideration as a DSM psychiatric disorder in discussions for DSM-5. Recent community prevalence studies suggest that skin picking disorder appears to be as common as many other psychiatric disorders, with reported prevalences ranging from 1.4% to 5.4%. Clinical evaluation of patients with skin picking disorder entails a broad physical and psychiatric examination, encouraging an interdisciplinary approach to evaluation and treatment. Approaches to treatment should include cognitive-behavioral therapy (including habit reversal or acceptance-enhanced behavior therapy) and medication (serotonin reuptake inhibitors, N-acetylcysteine, or naltrexone). Based on clinical experience and research findings, the authors recommend several management approaches to skin picking disorder. C1 [Grant, Jon E.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Trichotillomania Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Res Unit, Boston, MA 02114 USA. Univ Stellenbosch, Dept Psychiat, MRC Unit Anxiety & Stress Disorders, ZA-7600 Stellenbosch, South Africa. Univ Cape Town, Dept Psychiat & Mental Hlth, ZA-7700 Rondebosch, South Africa. RP Grant, JE (reprint author), Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. EM jongrant@uchicago.edu RI Odlaug, Brian/C-5586-2013; Chamberlain, Samuel/A-7839-2008; Stein, Dan/A-1752-2008 OI Odlaug, Brian/0000-0001-5407-0686; Chamberlain, Samuel/0000-0001-7014-8121; Stein, Dan/0000-0001-7218-7810 FU National Center for Responsible Gaming; Forest Pharmaceuticals; Psyadon Pharmaceuticals; Transcept Pharmaceuticals; University of South Florida; Oxford University Press; Norton; McGrawHill; Trichotillomania Learning Center; New Harbinger Publications; National Institute on Drug Abuse [1RC1DA028279-01] FX Dr. Grant has received research grants from the National Center for Responsible Gaming, Forest Pharmaceuticals, Psyadon Pharmaceuticals, Transcept Pharmaceuticals, and the University of South Florida, serves as the editor-in-chief of the Journal of Gambling Studies, and has received royalties from Oxford University Press, Norton, and McGrawHill. Mr. Odlaug has received research funding from the Trichotillomania Learning Center and honoraria from Oxford University Press and Current Medicine Group, LLC. Dr. Chamberlain has consulted for Cambridge Cognition, P1Vital, Shire, and Eli Lilly. Dr Keuthen has received research funding from the Trichotillomania Learning Center, has equity in Pfizer, Merck, GlaxoSmithKline, and Johnson di Johnson, and receives royalties from New Harbinger Publications. Drs. Stein and Lochner report no financial relationships with commercial interests.; Supported by a Center for Excellence in Gambling Research grant by the National Center for Responsible Gaming and an American Recovery and Reinvestment Act (ARRA) grant from the National Institute on Drug Abuse (1RC1DA028279-01) to Dr. Grant. NR 49 TC 34 Z9 35 U1 2 U2 29 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2012 VL 169 IS 11 BP 1143 EP 1149 DI 10.1176/appi.ajp.2012.12040508 PG 7 WC Psychiatry SC Psychiatry GA 031RA UT WOS:000310658400006 PM 23128921 ER PT J AU Hirshfeld-Becker, DR Micco, JA Henin, A Petty, C Faraone, SV Mazursky, H Bruett, L Rosenbaum, JF Biederman, J AF Hirshfeld-Becker, Dina R. Micco, Jamie A. Henin, Aude Petty, Carter Faraone, Stephen V. Mazursky, Heather Bruett, Lindsey Rosenbaum, Jerrold F. Biederman, Joseph TI Psychopathology in Adolescent Offspring of Parents With Panic Disorder, Major Depression, or Both: A 10-Year Follow-Up SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HIGH-RISK CHILDREN; PSYCHIATRIC-DISORDERS; ANXIETY; INTERVIEW; RELIABILITY; COMMUNITY; PATTERNS; MOTHERS; IMPACT; AGE AB Objective: The authors examined the specificity and course of psychiatric disorders from early childhood through adolescence in offspring of parents with confirmed panic disorder and major depressive disorder. Method: The authors examined rates of psychiatric disorders at 10-year-follow-up (mean age, 14 years) in four groups: offspring of referred parents with panic and depression (N=137), offspring of referred parents with panic without depression (N=26), offspring of referred parents with depression without panic (N=48), and offspring of nonreferred parents with neither disorder (N=80). Follow-up assessments relied on structured interviews with the adolescents and their mothers; diagnoses were rated present if endorsed by either. Results: Parental panic disorder, independently of parental depression, predicted lifetime rates in offspring of multiple anxiety disorders, panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Parental depression independently predicted offspring bipolar, drug use, and disruptive behavior disorders. Parental panic and depression interacted to predict specific phobia and major depressive disorder. Phobias were elevated in all at-risk groups, and depression was elevated in both offspring groups of parents with depression (with or without panic disorder), with the highest rates in the offspring of parents with depression only. Parental depression independently predicted new onset of depression, parental panic disorder independently predicted new onset of social phobia, and the two interacted to predict new onset of specific phobia and generalized anxiety disorder. Conclusions: At-risk offspring continue to develop new disorders as they progress through adolescence. These results support the need to screen and monitor the offspring of adults presenting for treatment of panic disorder or major depressive disorder. C1 [Hirshfeld-Becker, Dina R.] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Neurosci, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Physiol, Syracuse, NY USA. RP Hirshfeld-Becker, DR (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. EM dhirshfeld@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU AstraZeneca; Bristol-Myers Squibb; Forest Laboratories; Janssen; Lilly; McNeil Pediatrics; Pfizer; Pharmacia; Prechter Foundation; Sanofi-Aventis; Shire; Stanley Foundation; UCB Pharma; Wyeth; Oxford University Press.; Alcobra; Eli Lilly; NIH; McNeil; Novartis FX Drs. Hirshfeld-Becker, Henin, and Micco have received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported, in part, through independent medical education grants from pharmaceutical companies, including AstraZeneca, Bristol-Myers Squibb, Forest Laboratories, Janssen, Lilly, McNeil Pediatrics, Pfizer, Pharmacia, the Prechter Foundation, Sanofi-Aventis, Shire, the Stanley Foundation, UCB Pharma, and Wyeth. Dr. Henin also has received honoraria from Shire, Abbott Laboratories, and the American Academy of Child and Adolescent Psychiatry, has been a consultant for Pfizer, Prophase, and Concordant Rater Systems, and receives royalties from Oxford University Press. Dr. Faraone has served as a consultant or adviser to, received research support from, or participated in continuing medical education programs sponsored by Alcobra, Eli Lilly, Janssen, McNeil, NIH, Novartis, Otsuka, Pfizer, and Shire, and he receives royalties from Guilford Press and Oxford University Press. Dr. Biederman has received research support from Elminda, Janssen, McNeil, and Shire; speaking fees from Fundacion Areces (Spain), Fundacion Dr. Manuel Came lo A.C., Medice Pharmaceuticals, and the Spanish Child Psychiatry Association; consulting fees from Shionogi Pharma and Cipher Pharmaceuticals (honoraria were paid to the Department of Psychiatry at Massachusetts General Hospital [MGH]); honoraria from the MGH Psychiatry Academy for a tuition-funded CME course; an honorarium from Cambridge University Press for a chapter publication; and departmental royalties for a rating scale used for ADHD diagnosis (paid by Eli Lilly, Shire, and AstraZeneca to the Department of Psychiatry at MGH). Dr. Rosenbaum serves on the scientific advisory board of Medavante and has equity holdings at Medavante. The other authors report no financial relationships with commercial interests. NR 38 TC 12 Z9 12 U1 2 U2 23 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2012 VL 169 IS 11 BP 1175 EP 1184 DI 10.1176/appi.ajp.2012.11101514 PG 10 WC Psychiatry SC Psychiatry GA 031RA UT WOS:000310658400010 PM 23534056 ER PT J AU Megibow, AJ Sahani, D AF Megibow, Alec J. Sahani, Dushyant TI Best Practice: Implementation and Use of Abdominal Dual-Energy CT in Routine Patient Care SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE dual-energy CT; IV contrast; radiation; workflow ID COMPUTED-TOMOGRAPHY; ENHANCEMENT; FILTRATION; IMAGES AB OBJECTIVE. The purpose of this perspective is to document an experience with the adoption of dual-energy CT (DECT) for routine clinical imaging. CONCLUSION. Successful implementation of DECT requires that technologists understand standards of image quality, be empowered to select appropriate patients, and understand networks for image routing. Radiologists need minimal facility with workstations to access the information embedded in DECT. DECT can be performed at a reduced effective radiation dose compared with single-energy CT and with lower doses of IV contrast material. C1 [Megibow, Alec J.] NYU, Langone Med Ctr, Dept Radiol, New York, NY 10016 USA. [Sahani, Dushyant] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Megibow, AJ (reprint author), NYU, Langone Med Ctr, Dept Radiol, 550 1st Ave,Rm HCC 232, New York, NY 10016 USA. EM alec.megibow@nyumc.org NR 23 TC 20 Z9 20 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2012 VL 199 IS 5 SU S BP S71 EP S77 DI 10.2214/AJR.12.9074 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030SV UT WOS:000310591300010 PM 23097170 ER PT J AU Husain, SS Pejo, E Ge, R Raines, DE AF Husain, S. Shaukat Pejo, Ervin Ge, Rile Raines, Douglas E. TI Modifying Methoxycarbonyl Etomidate Inter-Ester Spacer Optimizes In Vitro Metabolic Stability and In Vivo Hypnotic Potency and Duration of Action SO ANESTHESIOLOGY LA English DT Article ID CNS 7056; INTRAVENOUS ANESTHESIA; ENZYMATIC-HYDROLYSIS; SPECIES-DIFFERENCES; CARBOXYLIC ESTERS; BLOOD ESTERASES; PHARMACOKINETICS; PHARMACODYNAMICS; SAFETY; ANALOG AB Background: Methoxycarbonyl etomidate is the prototypical very rapidly metabolized etomidate analog. Initial studies suggest that it may be too short acting for many clinical uses. We hypothesized that its duration of action could be lengthened and clinical utility broadened by incorporating specific aliphatic groups into the molecule to sterically protect its ester moiety from esterase-catalyzed hydrolysis. To test this hypothesis, we developed a series of methoxycarbonyl etomidate analogs (spacer-linked etomidate esters) containing various aliphatic-protecting groups and spacer lengths. Methods: Spacer-linked etomidate esters were synthesized and their hypnotic potencies and durations of action following bolus administration were measured in rats using a loss-of-righting reflexes assay. Octanol: water partition coefficients and metabolic half-lives in pooled rat blood were determined chromatographically. Results: All spacer-linked etomidate esters produced hypnosis rapidly and in a dose-dependent manner. ED(50)s for loss of righting reflexes ranged from 0.69 +/- 0.04 mg/kg for cyclopropyl-methoxycarbonyl metomidate to 11.1 +/- 0.8 mg/kg for methoxycarbonyl metomidate. The slope of a plot of the duration of loss of righting reflexes versus the logarithm of the dose ranged 12-fold among spacer-linked etomidate esters, implying widely varying brain clearance rates. The in vitro metabolic half-lives of these compounds in rat blood varied by more than two orders of magnitude and were diastereometrically selective. Conclusions: We created 13 new analogs of methoxycarbonyl etomidate and identified two that have significantly higher potency and potentially address the too-brief duration of action for methoxycarbonyl etomidate. This work may provide a blueprint for optimizing the pharmacological properties of other soft drugs. C1 [Husain, S. Shaukat; Pejo, Ervin; Ge, Rile; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@part-ners.org FU National Institutes of Health, Bethesda, Maryland [R01-GM087316, R21-DA029253]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital FX Supported by grant nos. R01-GM087316 and R21-DA029253 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. The Massachusetts General Hospital has submitted patent applications for methoxycarbonyl etomidate and related analogues. Two authors (Drs. Husain and Raines), and their respective laboratories, departments, and institutions could receive compensation related to the development or sale of the technology presented in this report. Dr. Raines is a consultant for and holds an equity interest in Annovation BioPharma Inc. (Cambridge, Massachusetts), which has licensed this technology for development. NR 23 TC 13 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2012 VL 117 IS 5 BP 1027 EP 1036 DI 10.1097/ALN.0b013e31826d3bef PG 10 WC Anesthesiology SC Anesthesiology GA 027DN UT WOS:000310332100017 PM 22929736 ER PT J AU Ge, R Pejo, E Husain, SS Cotten, JF Raines, DE AF Ge, Rile Pejo, Ervin Husain, S. Shaukat Cotten, Joseph F. Raines, Douglas E. TI Electroencephalographic and Hypnotic Recoveries after Brief and Prolonged Infusions of Etomidate and Optimized Soft Etomidate Analogs SO ANESTHESIOLOGY LA English DT Article ID REMIFENTANIL GI87084B; BURST SUPPRESSION; RATS; PHARMACOKINETICS; METABOLITE; ANESTHESIA; EEG AB Background: Methoxycarbonyl etomidate is the prototypical soft etomidate analog. Because it has relatively low potency and is extremely rapidly metabolized, large quantities must be infused to maintain hypnosis. Consequently with prolonged infusion, metabolite reaches sufficient concentrations to delay recovery. Dimethyl-methoxycarbonyl metomidate (DMMM) and cyclopropyl-methoxycarbonyl metomidate (CPMM) are methoxycarbonyl etomidate analogs with higher potencies and slower clearance. Because of these properties, we hypothesized that dosing would be lower and electroencephalographic and hypnotic recoveries would be faster - and less context-sensitive - with DMMM or CPMM versus methoxycarbonyl etomidate or etomidate. Methods: Etomidate, DMMM, and CPMM where infused into rats (n = 6 per group) for either 5 min or 120 min. After infusion termination, electroencephalographic and hypnotic recovery times were measured. The immobilizing ED50 infusion rates were determined using a tail clamp assay. Results: Upon terminating 5-min infusions, electroencephalographic and hypnotic recovery times were not different among hypnotics. However, upon terminating 120-min infusions, recovery times varied significantly with respective values (mean +/- SD) 48 +/- 13 min and 31 +/- 6.5 min (etomidate), 17 +/- 7.0 min and 14 +/- 3.4 min (DMMM), and 4.5 +/- 1.1 min and 4.2 +/- 1.6 min (CPMM). The immobilizing ED50 infusion rates were (mean +/- SD) 0.19 +/- 0.03 mg(-1) . kg(-1) . min(-1) (etomidate), 0.60 +/- 0.12 mg(-1) . kg(-1) . min(-1) (DMMM), and 0.89 +/- 0.18 mg(-1) . kg(-1) . min(-1) (CPMM). Conclusions: Electroencephalographic and hypnotic recoveries following prolonged infusions of DMMM and CPMM are faster than those following methoxycarbonyl etomidate or etomidate. In the case of CPMM infusion, recovery times are 4 min and context-insensitive. C1 [Ge, Rile; Pejo, Ervin; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,GRB444, Boston, MA 02114 USA. EM draines@partners.org FU National Institutes of Health, Bethesda, Maryland [R01-GM087316, R21-DA029253]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital FX Supported by grant nos. R01-GM087316 and R21-DA029253 from the National Institutes of Health, Bethesda, Maryland, and the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. The Massachusetts General Hospital has submitted patent applications for methoxycarbonyl etomidate and related analogs. Three authors (Drs. Husain, Cotten, and Raines), and their respective laboratories, departments, and institutions could receive compensation related to the development or sale of the technology presented in this report. Dr. Raines is a consultant for and holds an equity interest in Annovation BioPharma Inc. (Cambridge, Massachusetts), which has licensed this technology. NR 15 TC 10 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2012 VL 117 IS 5 BP 1037 EP 1043 DI 10.1097/ALN.0b013e31826d3de2 PG 7 WC Anesthesiology SC Anesthesiology GA 027DN UT WOS:000310332100018 PM 22929726 ER PT J AU Hanna, GM Weidman, JR Eikermann, M AF Hanna, George M. Weidman, J. Ren Eikermann, Matthias TI A Massive Upper Abdominal Tumor An Unusual Mechanism of Atelectasis and Cardiac Tamponade SO ANESTHESIOLOGY LA English DT Editorial Material C1 [Hanna, George M.; Weidman, J. Ren; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Hanna, George M.; Weidman, J. Ren; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. RP Hanna, GM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM meikermann@partners.org NR 2 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2012 VL 117 IS 5 BP 1129 EP 1129 DI 10.1097/ALN.0b013e3182531ccc PG 1 WC Anesthesiology SC Anesthesiology GA 027DN UT WOS:000310332100030 PM 22450475 ER PT J AU Kindler, HL Richards, DA Garbo, LE Garon, EB Stephenson, JJ Rocha-Lima, CM Safran, H Chan, D Kocs, DM Galimi, F McGreivy, J Bray, SL Hei, Y Feigal, EG Loh, E Fuchs, CS AF Kindler, H. L. Richards, D. A. Garbo, L. E. Garon, E. B. Stephenson, J. J., Jr. Rocha-Lima, C. M. Safran, H. Chan, D. Kocs, D. M. Galimi, F. McGreivy, J. Bray, S. L. Hei, Y. Feigal, E. G. Loh, E. Fuchs, C. S. TI A randomized, placebo-controlled phase 2 study of ganitumab (AMG 479) or conatumumab (AMG 655) in combination with gemcitabine in patients with metastatic pancreatic cancer SO ANNALS OF ONCOLOGY LA English DT Article DE AMG 479; conatumumab; ganitumab; gemcitabine; pancreatic cancer; phase 2 trial ID III TRIAL; ONCOLOGY-GROUP; ADENOCARCINOMA; APOPTOSIS; CAPECITABINE; MULTICENTER; BEVACIZUMAB; OXALIPLATIN; ACTIVATION; INTERGROUP AB We evaluated the efficacy and safety of ganitumab (a mAb antagonist of insulin-like growth factor 1 receptor) or conatumumab (a mAb agonist of human death receptor 5) combined with gemcitabine in a randomized phase 2 trial in patients with metastatic pancreatic cancer. Patients with a previously untreated metastatic pancreatic adenocarcinoma and an Eastern Cooperative Oncology Group (ECOG) performance status < 1 were randomized 1 : 1 : 1 to i.v. gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) combined with open-label ganitumab (12 mg/kg every 2 weeks [Q2W]), double-blind conatumumab (10 mg/kg Q2W), or double-blind placebo Q2W. The primary end point was 6-month survival rate. In total, 125 patients were randomized. The 6-month survival rates were 57% (95% CI 41-70) in the ganitumab arm, 59% (42-73) in the conatumumab arm, and 50% (33-64) in the placebo arm. The grade >= 3 adverse events in the ganitumab, conatumumab, and placebo arms, respectively, included neutropenia (18/22/13%), thrombocytopenia (15/17/8%), fatigue (13/12/5%), alanine aminotransferase increase (15/5/8%), and hyperglycemia (18/2/3%). Ganitumab combined with gemcitabine had tolerable toxicity and showed trends toward an improved 6-month survival rate and overall survival. Additional investigation into this combination is warranted. Conatumumab combined with gemcitabine showed some evidence of activity as assessed by the 6-month survival rate. C1 [Kindler, H. L.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Richards, D. A.] US Oncol Res, Tyler, TX USA. [Garbo, L. E.] US Oncol Res, Houston, TX USA. [Garon, E. B.] Univ Calif Los Angeles, David Geffen Sch Med, Translat Oncol Res Int Network, Los Angeles, CA 90095 USA. [Stephenson, J. J., Jr.] Greenville Hosp Syst Univ Med Ctr, Dept Expt Therapeut, Greenville, SC USA. [Rocha-Lima, C. M.] Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Safran, H.] Brown Univ, Rhode Isl Hosp, Oncol Grp, Providence, RI 02903 USA. [Chan, D.] Canc Care Associates Med Grp Inc, Redondo Beach, CA USA. [Kocs, D. M.] US Oncol Res, Round Rock, TX USA. [Galimi, F.; Hei, Y.; Feigal, E. G.] Amgen Inc, Global Dev, Thousand Oaks, CA 91320 USA. [McGreivy, J.; Loh, E.] Amgen Inc, Global Dev, San Francisco, CA USA. [Bray, S. L.] Amgen Ltd, Dept Biostat & Epidemiol, Cambridge, England. [Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Boston, MA 02115 USA. RP Kindler, HL (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM hkindler@medicine.bsd.uchicago.edu RI Galimi, Francesco/J-4238-2012 FU Amgen Inc. FX This work was supported by Amgen Inc. NR 37 TC 66 Z9 66 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2012 VL 23 IS 11 BP 2834 EP 2842 DI 10.1093/annonc/mds142 PG 9 WC Oncology SC Oncology GA 027SG UT WOS:000310373100010 PM 22700995 ER PT J AU Huober, J Gelber, S Goldhirsch, A Coates, AS Viale, G Ohlschlegel, C Price, KN Gelber, RD Regan, MM Thurlimann, B AF Huober, J. Gelber, S. Goldhirsch, A. Coates, A. S. Viale, G. Oehlschlegel, C. Price, K. N. Gelber, R. D. Regan, M. M. Thuerlimann, B. TI Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group (IBCSG) trials SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; histology; invasive ductal; medullary; prognosis ID ADJUVANT CHEMOTHERAPY; DUCTAL CARCINOMA; PRIMARY THERAPY; RISK-FACTORS; FOLLOW-UP; TAMOXIFEN; FEATURES; COMBINATION; EXPRESSION; PHENOTYPE AB To evaluate whether medullary breast cancer has a better prognosis compared with invasive ductal tumors. Among 12 409 patients, 127 were recorded as invasive medullary tumors and 8096 invasive ductal tumors. Medullary and ductal invasive tumors were compared with regard to stage, age at diagnosis, grade, hormone receptor status, peritumoral vascular invasion, and local and systemic treatment. Pattern of relapse, distant recurrence-free interval (DRFI), and overall survival (OS) were determined for both histological groups. Two cohorts were investigated: a full cohort including the pathologist-determined medullary histology without regard to any other tumor features and a cohort restricted to patients with ER-negative grade 3 tumors. Fourteen-year DRFI and OS percents for medullary tumors (n = 127) and invasive ductal tumors (n = 8096) of the full cohort were 76% and 64% [hazard ratio (HR) 0.52, P = 0.0005] and 66% and 57% (HR = 0.75, P = 0.03), respectively. For the restricted cohort, 14-year DRFI and OS percents for the medullary (n = 47) and invasive ductal tumors (n = 1407) were 89% and 63% (HR 0.24, P = 0.002) and 74% and 54% (HR = 0.55, P = 0.01), respectively. Competing risk analysis for DRFI favored medullary tumors (HR medullary/ductal = 0.32; 95% confidence interval = 0.13-0.78, P = 0.01). Medullary tumors have a favorable prognosis compared with invasive ductal tumors. C1 [Huober, J.; Thuerlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Huober, J.; Oehlschlegel, C.; Thuerlimann, B.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Gelber, S.; Gelber, R. D.; Regan, M. M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. [Gelber, S.; Price, K. N.; Gelber, R. D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Goldhirsch, A.] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, A.] Swiss Ctr Breast Hlth, St Anna Clin, Lugano, Switzerland. [Coates, A. S.] Univ Sydney, Int Breast Canc Study Grp, Sydney, NSW 2006, Australia. [Coates, A. S.] Univ Sydney, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW 2006, Australia. [Viale, G.] Univ Milan, European Inst Oncol, IBCSG Cent Pathol Off, Div Pathol & Lab Med, Milan, Italy. [Oehlschlegel, C.] Kantonsspital, Dept Pathol, St Gallen, Switzerland. [Gelber, R. D.; Regan, M. M.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Sch Med, Boston, MA 02115 USA. RP Huober, J (reprint author), Univ Dusseldorf, Dept Gynecol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM jens.huober@med.uni-duesseldorf.de FU Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK); Swedish Society for Cancer Research (Cancerfonden); Ludwig Institute for Cancer Research; Cancer League of Ticino FX We thank the patients, physicians, nurses, and data managers who participate in the International Breast Cancer Study Group trials. We thank Joie Celano for data management. Presented in part elsewhere: American Society of Clinical Oncology, June, 2010, general poster session. We also acknowledge support for the Cape Town participants from the Cancer Association of South Africa, for the St Gallen participants from the Foundation for Clinical Research of Eastern Switzerland (OSKK), and for the Gothenburg participants from the Swedish Society for Cancer Research (Cancerfonden).; This work was supported by the Ludwig Institute for Cancer Research and the Cancer League of Ticino and the continuing support for central coordination, data management, and statistics provided by the Swedish Cancer Society; the Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health and Medical Research Council); the Frontier Science and Technology Research Foundation; the Swiss Group for Clinical Cancer Research (SAKK); the Swiss Cancer League; and the United States National Institutes of Health (CA-75362). NR 47 TC 21 Z9 22 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2012 VL 23 IS 11 BP 2843 EP 2851 DI 10.1093/annonc/mds105 PG 9 WC Oncology SC Oncology GA 027SG UT WOS:000310373100011 PM 22707751 ER PT J AU Karlsson, P Cole, BF Chua, BH Price, KN Lindtner, J Collins, JP Kovacs, A Thurlimann, B Crivellari, D Castiglione-Gertsch, M Forbes, JF Gelber, RD Goldhirsch, A Gruber, G AF Karlsson, P. Cole, B. F. Chua, B. H. Price, K. N. Lindtner, J. Collins, J. P. Kovacs, A. Thuerlimann, B. Crivellari, D. Castiglione-Gertsch, M. Forbes, J. F. Gelber, R. D. Goldhirsch, A. Gruber, G. CA Int Breast Canc Study Grp TI Patterns and risk factors for locoregional failures after mastectomy for breast cancer: an International Breast Cancer Study Group report SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant treatment; breast cancer; locoregional recurrence; postmastectomy radiotherapy ID REGIONAL NODAL FAILURE; GROUP TRIALS I; ADJUVANT CHEMOTHERAPY; CONSERVATIVE SURGERY; POSTMASTECTOMY RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; PROGNOSTIC-SIGNIFICANCE; PREMENOPAUSAL WOMEN; RADIATION-THERAPY; COOPERATIVE-GROUP AB Rates and risk factors of local, axillary and supraclavicular recurrences can guide patient selection and target for postmastectomy radiotherapy (PMRT). Local, axillary and supraclavicular recurrences were evaluated in 8106 patients enrolled in 13 randomized trials. Patients received chemotherapy and/or endocrine therapy and mastectomy without radiotherapy. Median follow-up was 15.2 years. Ten-year cumulative incidence for chest wall recurrence of > 15% was seen in patients aged < 40 years (16.1%), with >= 4 positive nodes (16.5%) or 0-7 uninvolved nodes (15.1%); for supraclavicular failures > 10%: >= 4 positive nodes (10.2%); for axillary failures of > 5%: aged < 40 years (5.1%), unknown primary tumor size (5.2%), 0-7 uninvolved nodes (5.2%). In patients with 1-3 positive nodes, 10-year cumulative incidence for chest wall recurrence of > 15% were age < 40, peritumoral vessel invasion or 0-7 uninvolved nodes. Age, number of positive nodes and number of uninvolved nodes were significant parameters for each locoregional relapse site. PMRT to the chest wall and supraclavicular fossa is supported in patients with >= 4 positive nodes. With 1-3 positive nodes, chest wall PMRT may be considered in patients aged < 40 years, with 0-7 uninvolved nodes or with vascular invasion. The findings do not support PMRT to the dissected axilla. C1 [Karlsson, P.] Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, S-41345 Gothenburg, Sweden. [Cole, B. F.] Univ Vermont, Coll Engn & Math Sci, Dept Math & Stat, Burlington, VT 05405 USA. [Cole, B. F.; Price, K. N.; Gelber, R. D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Chua, B. H.] Peter MacCallum Canc Ctr, Dept Radiat Oncol, Melbourne, Vic, Australia. [Chua, B. H.] Univ Melbourne, Melbourne, Vic, Australia. [Price, K. N.; Gelber, R. D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Lindtner, J.] Inst Oncol, Ljubljana, Slovenia. [Collins, J. P.] Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. [Kovacs, A.] Sahlgrens Univ Hosp, Dept Pathol, Gothenburg, Sweden. [Thuerlimann, B.] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, B.] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Crivellari, D.] Ctr Riferimento Oncol, Dept Med Oncol, I-33081 Aviano, Italy. [Castiglione-Gertsch, M.] Univ Hosp Geneva, Gynecooncol Unit, Geneva, Switzerland. [Forbes, J. F.] Univ Newcastle, Australian New Zealand Breast Canc Trials Grp, Calvary Mater Newcastle, Newcastle, NSW 2300, Australia. [Gelber, R. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gelber, R. D.] Harvard Univ, Sch Med, Boston, MA USA. [Goldhirsch, A.] Swiss Ctr Breast Hlth, St Anna Clin, Lugano, Switzerland. [Gruber, G.] Klin Hirslanden, Inst Radiotherapie, Zurich, Switzerland. [Goldhirsch, A.] European Inst Oncol, Milan, Italy. RP Karlsson, P (reprint author), Univ Gothenburg, Sahlgrenska Univ Hosp, Sahlgrenska Acad, Dept Oncol,Inst Clin Sci, Dubbsgatan 14,5th Floor, S-41345 Gothenburg, Sweden. EM per.karlsson@oncology.gu.se FU Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); National Institutes of Health [CA-75362]; Swedish Cancer Society; Cancer Association of South Africa; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK) FX This work was supported (in part) by Swiss Group for Clinical Cancer Research; Frontier Science and Technology Research Foundation; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group (National Health Medical Research Council); National Institutes of Health (CA-75362); Swedish Cancer Society; Cancer Association of South Africa; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK). NR 44 TC 11 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2012 VL 23 IS 11 BP 2852 EP 2858 DI 10.1093/annonc/mds118 PG 7 WC Oncology SC Oncology GA 027SG UT WOS:000310373100012 PM 22776708 ER PT J AU Morgan, EA Kozono, DE Wang, Q Mery, CM Butrynski, JE Baldini, EH George, S Nascimento, AF Raut, CP AF Morgan, Elizabeth A. Kozono, David E. Wang, Qian Mery, Carlos M. Butrynski, James E. Baldini, Elizabeth H. George, Suzanne Nascimento, Alessandra F. Raut, Chandrajit P. TI Cutaneous Radiation-Associated Angiosarcoma of the Breast: Poor Prognosis in a Rare Secondary Malignancy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Connective-Tissue-Oncology-Society CY NOV 05-07, 2009 CL Miami, FL SP Connect Tissue Oncol Soc ID ATYPICAL VASCULAR-LESIONS; CANCER; RADIOTHERAPY; CARCINOMA; CONSERVATION; SURGERY; THERAPY; RISK; PROLIFERATIONS; EXPERIENCE AB Cutaneous radiation-associated angiosarcoma of the breast (CRAASBr) is a rare complication of radiation therapy (RT) administered for primary breast cancer treatment. Although case series have provided clinical and histological descriptions of this disease, to our knowledge, none have identified trends in presentation and treatments that may contribute to outcomes. Demographic, clinical, histopathologic, and outcomes data for all patients presenting with CRAASBr for treatment or consultation at our institution from 1987 to 2009 were reviewed. We identified 33 patients (median age at CRAASBr presentation 71.3 years, range 43.1-87.2 years; median latency period 73.5 months, range 39.6-148.5 months). The most common presentation was breast skin ecchymosis (55 %). In four patients, initial biopsy demonstrated atypical vascular lesions suspicious for, but not diagnostic of, angiosarcoma. All patients underwent mastectomy. Median local recurrence-free survival (LRFS), recurrence-free survival (RFS), and overall survival (OS) rates were 18.2, 13.0, and 48.5 months, respectively. Patients who underwent resection of all irradiated breast skin as part of the mastectomy trended toward a better median LRFS (80.8 vs. 10.0 months, p = 0.065), RFS (72.6 vs. 10.0 months, p = 0.098), and OS (not achieved vs. 29.0 months, p = 0.054). CRAASBr is a potentially devastating consequence of RT for breast cancer, with poor LRFS, RFS, and OS rates. Patients with ecchymotic skin lesions require biopsy. Atypical vascular lesions require careful evaluation to rule out CRAASBr. If the diagnosis is confirmed, radical surgery encompassing both the breast parenchyma and the at-risk radiated skin should be performed. C1 [Morgan, Elizabeth A.; Nascimento, Alessandra F.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Morgan, Elizabeth A.; Kozono, David E.; Wang, Qian; Mery, Carlos M.; Butrynski, James E.; Baldini, Elizabeth H.; George, Suzanne; Nascimento, Alessandra F.; Raut, Chandrajit P.] Harvard Univ, Sch Med, Boston, MA USA. [Kozono, David E.; Baldini, Elizabeth H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Wang, Qian] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mery, Carlos M.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. [Butrynski, James E.; George, Suzanne] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Mery, Carlos M.] Texas Childrens Hosp, Houston, TX 77030 USA. [Nascimento, Alessandra F.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Morgan, EA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM craut@partners.org OI Morgan, Elizabeth/0000-0001-5880-9337 NR 24 TC 19 Z9 20 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2012 VL 19 IS 12 BP 3801 EP 3808 DI 10.1245/s10434-012-2563-4 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 025VZ UT WOS:000310225700025 PM 22890593 ER PT J AU Kono, Y Muder, RR AF Kono, Yuriko Muder, Robert R. TI Identifying the Incidence of and Risk Factors for Reamputation Among Patients Who Underwent Foot Amputation SO ANNALS OF VASCULAR SURGERY LA English DT Article ID DIABETIC FOOT; LIMB; MORTALITY AB Background: Many patients who have lower-extremity amputations secondary to peripheral vascular disease or diabetes require reamputation eventually. This study was designed to identify the incidence of and risk factors for ipsilateral reamputation after forefoot amputation, to evaluate whether postoperative infection increases the risk of reamputation, and to evaluate whether the risk of reamputation was reduced by the duration of antimicrobial therapy after amputation. Methods: A retrospective analysis of patients who underwent foot amputation for nontraumatic reason from January 2002 to December 2004 at the Veterans Affairs Pittsburgh Healthcare System was performed. Results: Among 116 patients, 57(49.1%) had ipsilateral reamputation within 3 years after their first surgeries; 78.9% received reamputation in the first 6 months; 53 (45.7%) died within 3 years; and 16 (13.8%) developed postoperative infections. Upper level of amputation, long duration of hospitalization, insulin-dependent diabetes, and gangrene on physical examination on admission were risk factors for reamputation in univariate analysis. Gangrene (odds ratio: 3.81, 95% confidence interval: 1.60-9.12, P = 0.003) and insulin-dependent diabetes (odds ratio: 2.93, 95% confidence interval: 1.26-6.78, P = 0.012) were risk factors in multivariate analysis. Postoperative infection did not increase the risk of reamputation. Longer than 2-week course of antibiotic use after amputation did not prevent reamputation. Conclusions: Approximately one-half of patients required ipsilateral reamputation and died in 3 years. Gangrene on admission and history of insulin-dependent diabetes were significant risk factors (P = 0.003, P = 0.028). Long duration of antibiotic use after amputation and postoperative infection did not change the risk of reamputation. C1 [Kono, Yuriko; Muder, Robert R.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15240 USA. RP Muder, RR (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Div Infect Dis, Pittsburgh, PA 15240 USA. EM robert.muder@va.gov NR 12 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD NOV PY 2012 VL 26 IS 8 BP 1120 EP 1126 DI 10.1016/j.avsg.2012.02.011 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 028GB UT WOS:000310409700010 PM 22840342 ER PT J AU Wofsy, D Hillson, JL Diamond, B AF Wofsy, David Hillson, Jan L. Diamond, Betty TI Abatacept for lupus nephritis Alternative definitions of complete response support conflicting conclusions SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MURINE LUPUS; CYCLOPHOSPHAMIDE; ERYTHEMATOSUS; CLASSIFICATION; EFFICACY; THERAPY; CTLA4IG; SAFETY; TRIAL AB Objective Recent clinical trials in lupus nephritis have all used different criteria to assess complete response. The objective of this analysis was to compare several previously proposed criteria, using the same data set from a large trial of abatacept in lupus nephritis (IM101075). In so doing, we sought to determine which criteria are most sensitive to differences among treatment groups and to further examine the potential of abatacept in lupus nephritis. Methods Patients in the IM101075 trial received abatacept at 1 of 2 different dose regimens or placebo, both on a background of mycophenolate mofetil and corticosteroids. Using data from this trial, we assessed rates of complete response at 12 months according to 5 sets of criteria, from 1) the trial protocol, 2) the Aspreva Lupus Management Study (ALMS) trial of mycophenolate mofetil, 3) the Lupus Nephritis Assessment with Rituximab (LUNAR) trial of rituximab, 4) an ongoing National Institutes of Health trial of abatacept (Abatacept and Cyclophosphamide Combination: Efficacy and Safety Study [ACCESS]), and 5) published recommendations of the American College of Rheumatology. Results According to the complete response definition from the IM101075 study protocol, there was no difference among treatment groups in the IM101075 study. In contrast, according to the ALMS, LUNAR, and ACCESS criteria, rates of complete response among patients in the IM101075 study were higher in both treatment groups relative to control. The largest differences were obtained with use of the LUNAR criteria (complete response rate of 6% in the control group, compared to 22% and 24% in the 2 abatacept groups). Conclusion The choice of definition of complete response can determine whether a lupus nephritis trial is interpreted as a success or a failure. The results of this analysis provide an evidence-based rationale for choosing among alternative definitions and offer a strong rationale for conducting further studies of abatacept in lupus nephritis. C1 [Wofsy, David] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hillson, Jan L.] Bristol Myers Squibb Co, Princeton, NJ USA. [Diamond, Betty] Feinstein Inst Med Res, Manhasset, NY USA. RP Wofsy, D (reprint author), San Francisco VA Med Ctr, Arthritis Immunol Unit 111R, 4150 Clement St, San Francisco, CA 94121 USA. EM wofsyd@medsch.ucsf.edu FU Rosalind Russell Medical Research Center for Arthritis at the University of California, San Francisco; Bristol-Myers Squibb; Genentech; Vifor Pharma; Pfizer; Merck-Serono; Merck FX Supported by the Rosalind Russell Medical Research Center for Arthritis at the University of California, San Francisco.; Dr. Wofsy has received consulting fees from Bristol-Myers Squibb, Genentech, and Vifor Pharma (less than $10,000 each). Dr. Hillson owns stock or stock options in Bristol-Myers Squibb. Dr. Diamond has received consulting fees and/or honoraria from Genentech, Pfizer, Merck-Serono, and Merck (less than $10,000 each). Drs. Wofsy and Diamond were not compensated for this investigator-initiated analysis. NR 15 TC 72 Z9 74 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD NOV PY 2012 VL 64 IS 11 BP 3660 EP 3665 DI 10.1002/art.34624 PG 6 WC Rheumatology SC Rheumatology GA 030CC UT WOS:000310544500019 PM 22806274 ER PT J AU Unizony, S Arias-Urdaneta, L Miloslavsky, E Arvikar, S Khosroshahi, A Keroack, B Stone, JR Stone, JH AF Unizony, S. Arias-Urdaneta, L. Miloslavsky, E. Arvikar, S. Khosroshahi, A. Keroack, B. Stone, J. R. Stone, J. H. TI Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica SO ARTHRITIS CARE & RESEARCH LA English DT Article ID PLACEBO-CONTROLLED TRIAL; ANTI-INTERLEUKIN-6 RECEPTOR ANTIBODY; RHEUMATOLOGY 1990 CRITERIA; REGULATORY T-CELLS; TERM-FOLLOW-UP; DOUBLE-BLIND; RANDOMIZED-TRIAL; GLUCOCORTICOID THERAPY; INTERLEUKIN-6 BLOCKADE; DISEASE-ACTIVITY AB Objective The interleukin-6 pathway is up-regulated in giant cell arteritis (GCA), Takayasu arteritis (TA), and polymyalgia rheumatica (PMR). We retrospectively assessed the outcomes of 10 patients with relapsing/refractory GCA, TA, or PMR treated with tocilizumab (TCZ). Methods Patients with GCA (n = 7), TA (n = 2), and PMR (n = 1) received TCZ. Seven subjects had failed at least 1 second-line agent. The outcomes evaluated were symptoms of disease activity, inflammatory markers, ability to taper glucocorticoids, and cross-sectional imaging when indicated clinically. Results The mean followup time of this cohort since diagnosis was 27 months (range 1660 months). The patients were treated with TCZ for a mean period of 7.8 months (range 412 months). Before TCZ therapy, the patients experienced an average of 2.4 flares/year. All patients entered and maintained clinical remission during TCZ therapy. The mean daily prednisone dosages before and after TCZ initiation were 20.8 mg/day (range 734.3 mg/day) and 4.1 mg/day (range 010.7 mg/day), respectively (P = 0.0001). The mean erythrocyte sedimentation rate declined from 41.5 mm/hour (range 1168 mm/hour) to 7 mm/hour (range 2.211.3 mm/hour; P = 0.0001). The adverse effects of TCZ included mild neutropenia (n = 4) and transaminitis (n = 4). One patient flared 2 months after TCZ discontinuation. An autopsy on 1 patient who died from a postoperative myocardial infarction following elective surgery revealed persistent vasculitis of large and medium-sized arteries. Conclusion TCZ therapy led to clinical and serologic improvement in patients with refractory/relapsing GCA, TA, or PMR. The demonstration of persistent large-vessel vasculitis at autopsy of 1 patient who had shown a substantial response requires close scrutiny in larger studies. C1 [Stone, J. H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Unizony, S.; Arias-Urdaneta, L.; Miloslavsky, E.; Arvikar, S.; Khosroshahi, A.; Stone, J. R.; Stone, J. H.] Harvard Univ, Sch Med, Boston, MA USA. [Keroack, B.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Keroack, B.] Rheumatol Associates, Maine Med Ctr, Portland, ME USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit Street,Yawkey 2C, Boston, MA 02114 USA. EM jhstone@partners.org FU Roche FX Dr. J. H. Stone has received consultancy fees, speaking fees, and/or honoraria (more than $10,000) from Roche. NR 55 TC 94 Z9 96 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2012 VL 64 IS 11 BP 1720 EP 1729 DI 10.1002/acr.21750 PG 10 WC Rheumatology SC Rheumatology GA 030CH UT WOS:000310545000012 PM 22674883 ER PT J AU Schwab, P Harmon, D Bruno, R Fraunfelder, FW Kim, DH AF Schwab, Pascale Harmon, David Bruno, Richard Fraunfelder, Frederick W. Kim, Donna Hyunchung TI A 55-year-old woman with orbital inflammation SO ARTHRITIS CARE & RESEARCH LA English DT Article ID METASTATIC PROSTATE-CANCER; ZOLEDRONIC ACID INFUSION; ACUTE-PHASE RESPONSE; GRAVES OPHTHALMOPATHY; OCULAR INFLAMMATION; RISK-FACTORS; DISEASE; PAMIDRONATE; SARCOIDOSIS; ACTIVATION C1 [Schwab, Pascale] Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. [Schwab, Pascale] Portland VA Med Ctr, Portland, OR USA. RP Schwab, P (reprint author), Oregon Hlth & Sci Univ, Div Arthrit & Rheumat Dis, Portland Vet Affairs Med Ctr, 3181 SW Sam Jackson Pk Rd OP09, Portland, OR 97239 USA. EM schwabp@ohsu.edu OI Bruno, Richard/0000-0001-9803-2876 NR 42 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD NOV PY 2012 VL 64 IS 11 BP 1776 EP 1782 DI 10.1002/acr.21822 PG 7 WC Rheumatology SC Rheumatology GA 030CH UT WOS:000310545000020 PM 22933406 ER PT J AU Banerjee, S Xu, H Fuh, E Nguyen, KT Garcia, JA Brilakis, ES Bhatt, DL AF Banerjee, Subhash Xu, Hao Fuh, Eric Nguyen, Kytai T. Garcia, Joseph A. Brilakis, Emmanouil S. Bhatt, Deepak L. TI Endothelial progenitor cell response to antiproliferative drug exposure SO ATHEROSCLEROSIS LA English DT Article DE Endothelial progenitor cell; Antiproliferative drugs; Drug-eluting stent ID OPTICAL COHERENCE TOMOGRAPHY; BARE-METAL STENTS; SIROLIMUS-ELUTING STENTS; NEOINTIMAL COVERAGE; NETWORK METAANALYSIS; PACLITAXEL; IMPLANTATION; THROMBOSIS; RESTENOSIS AB Background: Vascular stent coverage by endothelial cells, derived from endothelial progenitor cells (EPC) is considered a surrogate for healing. However, the effects of antiproliferative drugs used in current drug-eluting stents (DES) on EPC proliferative and antithrombotic function remains poorly defined. Method and results: Herein, we studied and compared the in vitro and in vivo effects of four antiproliferative drugs - paclitaxel, sirolimus, everolimus, and zotarolimus on several EPC properties including colony forming units (CFU), cell proliferation, apoptosis, antithrombotic and prothrombotic gene expression and nitric oxide (NO) as well as prostacyclin (PGI(2)) release. We also examined EPC migration and adhesion under flow conditions. We find that whereas all antiproliferative agents inhibited EPC proliferation and caused cell apoptosis, only paclitaxel and sirolimus reduced CFU formation. Paclitaxel treatment also resulted in the greatest down-regulation of antithrombotic gene expression and up-regulation of prothrombotic gene expression. NO release, migration, and adhesion of EPC under shear stress were inhibited by all antiproliferative drugs, most notably by paclitaxel and sirolimus. Conclusions: These results indicate that antiproliferative drugs on DES, particularly paclitaxel, impair the proliferative and antithrombotic functions of EPC, and thereby could contribute to incomplete vascular healing and increase the risk of stent thrombosis. Published by Elsevier Ireland Ltd. C1 [Banerjee, Subhash; Xu, Hao; Garcia, Joseph A.; Brilakis, Emmanouil S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75216 USA. [Banerjee, Subhash; Fuh, Eric; Garcia, Joseph A.; Brilakis, Emmanouil S.] Vet Affairs N Texas Vet Hlth Care Ctr, Dallas, TX USA. [Nguyen, Kytai T.] Univ Texas Arlington, Arlington, TX 76019 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Banerjee, S (reprint author), Univ Texas SW Med Ctr Dallas, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM subhash.banerjee@utsouthwestern.edu OI Brilakis, Emmanouil/0000-0001-9416-9701 FU Medicines Company; Gilead; Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis FX S Banerjee has received speaker honoraria from Medtronic, Covidien and research support from Medicines Company and Gilead; DL Bhatt is on the advisory board of: Medscape Cardiology; board of directors: Boston VA Research Institute, Society of Chest Pain Centers; chair: American Heart Association Get With The Guidelines Science Subcommittee; honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); research grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; unfunded research: PLx Pharma, Takeda. H Xu, E Fuh, KT Nguyen, JA Garcia have no disclosures. NR 30 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD NOV PY 2012 VL 225 IS 1 BP 91 EP 98 DI 10.1016/j.atherosclerosis.2012.08.025 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 027LO UT WOS:000310354000014 PM 22959701 ER PT J AU Magalhaes, PV Dodd, S Nierenberg, AA Berk, M AF Magalhaes, Pedro Vieira Dodd, Seetal Nierenberg, Andrew A. Berk, Michael TI Cumulative morbidity and prognostic staging of illness in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Bipolar disorder; cumulative morbidity; longitudinal; prognosis; staging ID RANDOMIZED CONTROLLED-TRIAL; 5-YEAR FOLLOW-UP; EARLY INTERVENTION; MOOD DISORDERS; STANDARD TREATMENT; ALLOSTATIC LOAD; MENTAL-HEALTH; MODELS; NEUROPROGRESSION; PSYCHIATRY AB Objective: Staging models may provide heuristic utility for intervention selection in psychiatry. Although a few proposals have been put forth, there is a need for empirical validation if they are to be adopted. Using data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), we tested a previously elaborated hypothesis on the utility of using the number of previous episodes as a relevant prognostic variable for staging in bipolar disorder. Methods: This report utilizes data from the multisite, prospective, open-label study 'Standard Care Pathways' and the subset of patients with acute depressive episodes who participated in the randomized trial of adjunctive antidepressant treatment. Outpatients meeting DSM-IV diagnostic criteria for bipolar disorder (n = 3345) were included. For the randomized pathway, patients met criteria for an acute depressive episode (n = 376). The number of previous episodes was categorized as less than 5, 5-10 and more than 10. We used disability at baseline, number of days well in the first year and longitudinal scores of depressive and manic symptoms, quality of life and functioning as validators of models constructed a priori. Results: Patients with multiple previous episodes had consistently poorer cross-sectional and prospective outcomes. Functioning and quality of life were worse, disability more common, and symptoms more chronic and severe. There was no significant effect for staging with regard to antidepressant response in the randomized trial. Conclusions: These findings confirm that bipolar disorder can be staged with prognostic validity. Stages can be used to stratify subjects in clinical trials and develop specific treatments. C1 [Magalhaes, Pedro Vieira] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Natl Inst Translat Med, Porto Alegre, RS, Brazil. [Magalhaes, Pedro Vieira; Dodd, Seetal; Berk, Michael] Univ Melbourne, Dept Psychiat, Parkville, Vic 3052, Australia. [Dodd, Seetal; Berk, Michael] Deakin Univ, Sch Med, Barwon Hlth, Geelong, Vic 3217, Australia. [Nierenberg, Andrew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Berk, Michael] Orygen Youth Hlth Res Ctr, Parkville, Vic, Australia. [Berk, Michael] Florey Inst Neurosci & Mental Hlth, Parkville, Vic, Australia. RP Berk, M (reprint author), Univ Melbourne, Dept Clin & Biomed Sci, Barwon Hlth, POB 281, Geelong, Vic 3220, Australia. EM mikebe@barwonhealth.org.au RI Magalhaes, Pedro/A-8519-2008; Berk, Michael/M-7891-2013 OI Magalhaes, Pedro/0000-0002-5644-6357; Berk, Michael/0000-0002-5554-6946 FU NIH; Cooperative Research Centre; Simons Autism Foundation; Cancer Council of Victoria; Stanley Medical Research Foundation; MBF; NHMRC; Beyond Blue; Rotary Health; Geelong Medical Research Foundation; Bristol Myers Squibb; Eli Lilly; Glaxo SmithKline; Organon; Novartis; Mayne Pharma; Servier FX MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Organon, Novartis, Mayne Pharma and Servier, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth, and served as a consultant to Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck Merck and Servier. NR 65 TC 23 Z9 25 U1 2 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD NOV PY 2012 VL 46 IS 11 BP 1058 EP 1067 DI 10.1177/0004867412460593 PG 10 WC Psychiatry SC Psychiatry GA 026NJ UT WOS:000310285900007 PM 23015748 ER PT J AU Feng, JX Meyer, CA Wang, Q Liu, JS Liu, XS Zhang, Y AF Feng, Jianxing Meyer, Clifford A. Wang, Qian Liu, Jun S. Liu, X. Shirley Zhang, Yong TI GFOLD: a generalized fold change for ranking differentially expressed genes from RNA-seq data SO BIOINFORMATICS LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; SEQUENCE COUNT DATA; PROGNOSTIC-SIGNIFICANCE; GROWTH-FACTOR; HUMAN GENOME; TRANSCRIPTOME; TECHNOLOGIES; RESOLUTION; PACKAGE; CELLS AB Motivation: RNA-seq has been widely used in transcriptome analysis to effectively measure gene expression levels. Although sequencing costs are rapidly decreasing, almost 70% of all the human RNA-seq samples in the gene expression omnibus do not have biological replicates and more unreplicated RNA-seq data were published than replicated RNA-seq data in 2011. Despite the large amount of single replicate studies, there is currently no satisfactory method for detecting differentially expressed genes when only a single biological replicate is available. Results: We present the GFOLD (generalized fold change) algorithm to produce biologically meaningful rankings of differentially expressed genes from RNA-seq data. GFOLD assigns reliable statistics for expression changes based on the posterior distribution of log fold change. In this way, GFOLD overcomes the shortcomings of P-value and fold change calculated by existing RNA-seq analysis methods and gives more stable and biological meaningful gene rankings when only a single biological replicate is available. C1 [Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Cambridge, MA 02138 USA. [Liu, Jun S.] Harvard Univ, Dept Stat, Sci Ctr 715, Cambridge, MA 02138 USA. [Feng, Jianxing; Wang, Qian; Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 20092, Peoples R China. [Feng, Jianxing] Fudan Univ, Shanghai Key Lab Intelligent Informat Proc, Shanghai 200433, Peoples R China. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Cambridge, MA 02138 USA. EM xsliu@jimmy.harvard.edu; yzhang@tongji.edu.cn RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU The National Basic Research Program of China (973 Program) [2010CB944904, 2011CB965104]; National Natural Science Foundation of China [31028011, 31071114]; Shanghai Rising-Star Program [10QA1407300]; New Century Excellent Talents in the University of China [NCET-11-0389]; Shanghai Key Laboratory of Intelligent Information Processing of China [20102662]; Excellent Young Teachers Program of Tongji University [2010KJ041]; Innovative Research Team Program Ministry of Education of China [IRT1168] FX The National Basic Research Program of China (973 Program; 2010CB944904 and 2011CB965104), the National Natural Science Foundation of China (31028011 and 31071114), the Shanghai Rising-Star Program (10QA1407300), the New Century Excellent Talents in the University of China (NCET-11-0389), Shanghai Key Laboratory of Intelligent Information Processing of China (20102662), the Excellent Young Teachers Program of Tongji University (2010KJ041) and the Innovative Research Team Program Ministry of Education of China (IRT1168). NR 39 TC 80 Z9 82 U1 0 U2 37 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2012 VL 28 IS 21 BP 2782 EP 2788 DI 10.1093/bioinformatics/bts515 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 025AR UT WOS:000310155300010 PM 22923299 ER PT J AU Schwartz, A Weiner, SJ Weaver, F Yudkowsky, R Sharma, G Binns-Calvey, A Preyss, B Jordan, N AF Schwartz, Alan Weiner, Saul J. Weaver, Frances Yudkowsky, Rachel Sharma, Gunjan Binns-Calvey, Amy Preyss, Ben Jordan, Neil TI Uncharted territory: measuring costs of diagnostic errors outside the medical record SO BMJ QUALITY & SAFETY LA English DT Article ID UNANNOUNCED STANDARDIZED PATIENTS; PHYSICIAN PERFORMANCE; CLINICAL VIGNETTES; CONTEXTUAL ERRORS; CHART ABSTRACTION; PRIMARY-CARE; QUALITY AB Context: In a past study using unannounced standardised patients (USPs), substantial rates of diagnostic and treatment errors were documented among internists. Because the authors know the correct disposition of these encounters and obtained the physicians' notes, they can identify necessary treatment that was not provided and unnecessary treatment. They can also discern which errors can be identified exclusively from a review of the medical records. Objective: To estimate the avoidable direct costs incurred by physicians making errors in our previous study. Design: In the study, USPs visited 111 internal medicine attending physicians. They presented variants of four previously validated cases that jointly manipulate the presence or absence of contextual and biomedical factors that could lead to errors in management if overlooked. For example, in a patient with worsening asthma symptoms, a complicating biomedical factor was the presence of reflux disease and a complicating contextual factor was inability to afford the currently prescribed inhaler. Costs of missed or unnecessary services were computed using Medicare cost-based reimbursement data. Setting: Fourteen practice locations, including two academic clinics, two community-based primary care networks with multiple sites, a core safety net provider, and three Veteran Administration government facilities. Main outcome measures: Contribution of errors to costs of care. Results: Overall, errors in care resulted in predicted costs of approximately $174000 across 399 visits, of which only $8745 was discernible from a review of the medical records alone (without knowledge of the correct diagnoses). The median cost of error per visit with an incorrect care plan differed by case and by presentation variant within case. Conclusions: Chart reviews alone underestimate costs of care because they typically reflect appropriate treatment decisions conditional on (potentially erroneous) diagnoses. Important information about patient context is often entirely missing from medical records. Experimental methods, including the use of USPs, reveal the substantial costs of these errors. C1 [Schwartz, Alan; Yudkowsky, Rachel; Binns-Calvey, Amy] Univ Illinois, Dept Med Educ, Chicago, IL 60612 USA. [Weiner, Saul J.; Jordan, Neil] Univ Illinois, US Dept Vet Affairs, Ctr Management Complex Chron Care, Chicago, IL 60612 USA. [Weaver, Frances] Loyola Univ, Stritch Sch Med, US Dept Vet Affairs, Ctr Management Complex Chron Care, Chicago, IL 60611 USA. [Sharma, Gunjan] Univ Illinois, Dept Med, Chicago, IL 60612 USA. [Preyss, Ben] Northwestern Univ, Dept Family Med, Chicago, IL 60611 USA. [Jordan, Neil] Northwestern Univ, Feinberg Sch Med, Inst Healthcare Studies & Prevent Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. RP Schwartz, A (reprint author), Univ Illinois, Dept Med Educ, 808 S Wood St,986 CME Mail Code 591, Chicago, IL 60612 USA. EM alansz@uic.edu RI Binns, Colin/A-6012-2008; OI Yudkowsky, Rachel/0000-0002-2145-7582; Schwartz, Alan/0000-0003-3809-6637 FU Veteran Affairs, Health Services Research and Development [04-107] FX This study was supported by the Veteran Affairs, Health Services Research and Development. The funding organisation had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review or approval of the manuscript. IIR 04-107. NR 19 TC 7 Z9 7 U1 0 U2 6 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD NOV PY 2012 VL 21 IS 11 BP 918 EP 924 DI 10.1136/bmjqs-2012-000832 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 028VE UT WOS:000310451400005 PM 22773889 ER PT J AU Ancukiewicz, M Miller, CL Skolny, MN O'Toole, J Warren, LE Jammallo, LS Specht, MC Taghian, AG AF Ancukiewicz, Marek Miller, Cynthia L. Skolny, Melissa N. O'Toole, Jean Warren, Laura E. Jammallo, Lauren S. Specht, Michelle C. Taghian, Alphonse G. TI Comparison of relative versus absolute arm size change as criteria for quantifying breast cancer-related lymphedema: the flaws in current studies and need for universal methodology (vol 135, pg 145, 2012) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Correction C1 [Ancukiewicz, Marek; Miller, Cynthia L.; Skolny, Melissa N.; Warren, Laura E.; Jammallo, Lauren S.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Specht, Michelle C.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. EM ataghian@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2012 VL 136 IS 2 BP 623 EP 623 DI 10.1007/s10549-012-2241-z PG 1 WC Oncology SC Oncology GA 027UG UT WOS:000310378700034 ER PT J AU Dummer, R Tsao, H Robert, C AF Dummer, R. Tsao, H. Robert, C. TI How cutaneous eruptions help to understand the mode of action of kinase inhibitors SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Editorial Material ID GROWTH-FACTOR RECEPTOR; ADVANCED MELANOMA; IMPROVED SURVIVAL; RAS MUTATIONS; BRAF; CANCER; TRIAL; VEMURAFENIB; DABRAFENIB; TUMORS C1 [Dummer, R.] Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. [Tsao, H.] Massachusetts Gen Hosp, MGH Melanoma & Pigmented Lesion Ctr, Boston, MA 02114 USA. [Robert, C.] Inst Gustave Roussy, INSERM, U981, F-94805 Villejuif Paris Sud, France. RP Dummer, R (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM reinhard.dummer@usz.ch NR 22 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2012 VL 167 IS 5 BP 965 EP 967 DI 10.1111/bjd.12080 PG 3 WC Dermatology SC Dermatology GA 030BI UT WOS:000310542200001 PM 23106351 ER PT J AU Wanderer, JP Rao, AV Rothwell, SH Ehrenfeld, JM AF Wanderer, Jonathan P. Rao, Anoop V. Rothwell, Sarah H. Ehrenfeld, Jesse M. TI Comparing two anesthesia information management system user interfaces: a usability evaluation SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID TASK-ANALYSIS; DOCUMENTATION; DISPLAY; PERFORMANCE; RECORDS; SIMULATION; ADOPTION; DESIGN AB Anesthesia information management systems (AIMS) have been developed by multiple vendors and are deployed in thousands of operating rooms around the world, yet not much is known about measuring and improving AIMS usability. We developed a methodology for evaluating AIMS usability in a low-fidelity simulated clinical environment and used it to compare an existing user interface with a revised version. We hypothesized that the revised user interface would be more useable. In a low-fidelity simulated clinical environment, twenty anesthesia providers documented essential anesthetic information for the start of the case using both an existing and a revised user interface. Participants had not used the revised user interface previously and completed a brief training exercise prior to the study task. All participants completed a workload assessment and a satisfaction survey. All sessions were recorded. Multiple usability metrics were measured. The primary outcome was documentation accuracy. Secondary outcomes were perceived workload, number of documentation steps, number of user interactions, and documentation time. The interfaces were compared and design problems were identified by analyzing recorded sessions and survey results. Use of the revised user interface was shown to improve documentation accuracy from 85.1% to 92.4%, a difference of 7.3% (95% confidence interval [CI] for the difference 1.8 to 12.7). The revised user interface decreased the number of user interactions by 6.5 for intravenous documentation (95% CI 2.9 to 10.1) and by 16.1 for airway documentation (95% CI 11.1 to 21.1). The revised user interface required 3.8 fewer documentation steps (95% CI 2.3 to 5.4). Airway documentation time was reduced by 30.5 seconds with the revised workflow (95% CI 8.5 to 52.4). There were no significant time differences noted in intravenous documentation or in total task time. No difference in perceived workload was found between the user interfaces. Two user interface design problems were identified in the revised user interface. The usability of anesthesia information management systems can be evaluated using a low-fidelity simulated clinical environment. User testing of the revised user interface showed improvement in some usability metrics and highlighted areas for further revision. Vendors of AIMS and those who use them should consider adopting methods to evaluate and improve AIMS usability. C1 [Wanderer, Jonathan P.; Ehrenfeld, Jesse M.] Vanderbilt Univ, Nashville, TN 37212 USA. [Rao, Anoop V.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain, Boston, MA 02114 USA. RP Wanderer, JP (reprint author), Vanderbilt Univ, 1301 Med Ctr Dr,TVC 4648, Nashville, TN 37212 USA. EM Jonathan.p.wanderer@vanderbilt.edu OI Ehrenfeld, Jesse/0000-0003-3427-0140 FU National Institute of Health [5T32GM007592]; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital FX Financial support for the conduct of this clinical trial was provided by 5T32GM007592 from the National Institute of Health, as well as by department funds of the Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital. NR 24 TC 7 Z9 7 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANESTH JI Can. J. Anesth. PD NOV PY 2012 VL 59 IS 11 BP 1023 EP 1031 DI 10.1007/s12630-012-9771-z PG 9 WC Anesthesiology SC Anesthesiology GA 027GM UT WOS:000310340200003 PM 23055030 ER PT J AU Keeyapaj, W Alfirevic, A AF Keeyapaj, Worasak Alfirevic, Andrej TI Carinal resection using an airway exchange catheter-assisted venovenous ECMO technique SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Letter C1 [Keeyapaj, Worasak] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Alfirevic, Andrej] Cleveland Clin, Cleveland, OH 44106 USA. RP Keeyapaj, W (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM kworasak@yahoo.com NR 4 TC 5 Z9 5 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X J9 CAN J ANESTH JI Can. J. Anesth. PD NOV PY 2012 VL 59 IS 11 BP 1075 EP 1076 DI 10.1007/s12630-012-9773-x PG 2 WC Anesthesiology SC Anesthesiology GA 027GM UT WOS:000310340200012 PM 22956288 ER PT J AU Pishvaian, MJ Marshall, JL Wagner, AJ Hwang, JJ Malik, S Cotarla, I Deeken, JF He, AR Daniel, H Halim, AB Zahir, H Copigneaux, C Liu, KJ Beckman, RA Demetri, GD AF Pishvaian, Michael J. Marshall, John L. Wagner, Andrew J. Hwang, Jimmy J. Malik, Shakun Cotarla, Ion Deeken, John F. He, A. Ruth Daniel, Hirut Halim, Abdel-Baset Zahir, Hamim Copigneaux, Catherine Liu, Kejian Beckman, Robert A. Demetri, George D. TI A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies SO CANCER LA English DT Article DE efatutazone; CS-7017; PPAR; phase 1; retinoid; biomarker ID HUMAN PROSTATE-CANCER; PPAR-GAMMA; CELL-GROWTH; COLORECTAL-CANCER; COLON-CANCER; DIFFERENTIATION; LIPOSARCOMA; INHIBITION; EXPRESSION; LIGAND AB BACKGROUND: Efatutazone (CS-7017), a novel peroxisome proliferator-activated receptor gamma (PPAR?) agonist, exerts anticancer activity in preclinical models. The authors conducted a phase 1 study to determine the recommended phase 2 dose, safety, tolerability, and pharmacokinetics of efatutazone. METHODS: Patients with advanced solid malignancies and no curative therapeutic options were enrolled to receive a given dose of efatutazone, administered orally (PO) twice daily for 6 weeks, in a 3 + 3 intercohort dose-escalation trial. After the third patient, patients with diabetes mellitus were excluded. Efatutazone dosing continued until disease progression or unacceptable toxicity, with measurement of efatutazone pharmacokinetics and plasma adiponectin levels. RESULTS: Thirty-one patients received efatutazone at doses ranging from 0.10 to 1.15 mg PO twice daily. Dose escalation stopped when maximal impact on PPAR?-related biomarkers had been reached before any protocol-defined maximum-tolerated dose level. On the basis of a population pharmacokinetic/pharmacodynamic analysis, the recommended phase 2 dose was 0.5 mg PO twice daily. A majority of patients experienced peripheral edema (53.3%), often requiring diuretics. Three episodes of dose-limiting toxicities, related to fluid retention, were noted in the 0.10-, 0.25-, and 1.15-mg cohorts. Of 31 treated patients, 27 were evaluable for response. A sustained partial response (PR; 690 days on therapy) was observed in a patient with myxoid liposarcoma. Ten additional patients had stable disease (SD) for =60 days. Exposures were approximately dose proportional, and adiponectin levels increased after 4 weeks of treatment at all dose levels. Immunohistochemistry of archived specimens demonstrated that PPAR? and retinoid X receptor expression levels were significantly greater in patients with SD for =60 days or PR (P = .0079), suggesting a predictive biomarker. CONCLUSIONS: Efatutazone demonstrates acceptable tolerability with evidence of disease control in patients with advanced malignancies. Cancer 2012. (c) 2012 American Cancer Society. C1 [Pishvaian, Michael J.; Marshall, John L.; Hwang, Jimmy J.; Malik, Shakun; Cotarla, Ion; Deeken, John F.; He, A. Ruth; Daniel, Hirut] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dev Therapeut Program, Med Ctr, Washington, DC 20007 USA. [Wagner, Andrew J.; Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA USA. [Halim, Abdel-Baset; Zahir, Hamim] Daiichi Sankyo Pharmaceut Dev, Translat Med & Clin Pharmacol, Edison, NJ USA. [Copigneaux, Catherine; Beckman, Robert A.] Daiichi Sankyo Pharmaceut Dev, Oncol Clin Res & Dev, Edison, NJ USA. [Liu, Kejian] Daiichi Sankyo Pharmaceut Dev, Biostat, Edison, NJ USA. RP Pishvaian, MJ (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dev Therapeut Program, Med Ctr, Podium B,3800 Reservoir Rd NW, Washington, DC 20007 USA. EM pishvaim@georgetown.edu FU Daiichi Sankyo Pharmaceutical Development FX This study and editorial support were sponsored by Daiichi Sankyo Pharmaceutical Development. NR 32 TC 25 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2012 VL 118 IS 21 BP 5403 EP 5413 DI 10.1002/cncr.27526 PG 11 WC Oncology SC Oncology GA 024BQ UT WOS:000310083000026 PM 22570147 ER PT J AU Ramalingam, SS Shaw, AT AF Ramalingam, Suresh S. Shaw, Alice T. TI Hypogonadism related to crizotinib therapy SO CANCER LA English DT Editorial Material ID CELL LUNG-CANCER; EML4-ALK; GENE C1 [Ramalingam, Suresh S.] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA. [Shaw, Alice T.] Harvard Univ, Sch Med, Boston, MA USA. [Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Ramalingam, SS (reprint author), Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, 1365 Clifton Rd,C-3090, Atlanta, GA 30322 USA. EM Suresh.Ramalingam@emory.edu FU NCI NIH HHS [U10 CA180864] NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2012 VL 118 IS 21 BP E1 EP E2 DI 10.1002/cncr.27561 PG 2 WC Oncology SC Oncology GA 024BQ UT WOS:000310083000001 PM 22487894 ER PT J AU Laird, JR Yeo, KK Rocha-Singh, K Das, T Joye, J Dippel, E Reddy, B Botti, C Jaff, MR AF Laird, John R., Jr. Yeo, Khung Keong Rocha-Singh, Krishna Das, Tony Joye, James Dippel, Eric Reddy, Bhagat Botti, Charles Jaff, Michael R. TI Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: Twelve-Month Results From the SALVAGE Study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE arteriolosclerosis; atherosclerosis; peripheral arterial disease; angioplasty; balloon; laser-assisted ID SUPERFICIAL-FEMORAL-ARTERY; NITINOL STENTS; INITIAL-EXPERIENCE; OCCLUSIVE DISEASE; CLINICAL-TRIALS; LESIONS; ATHERECTOMY; ISCHEMIA; IMPLANTATION; OBSTRUCTIONS AB Objectives The aim of the study is to evaluate the safety and effectiveness of treating femoropopliteal in-stent restenosis (ISR) with debulking with excimer laser followed by implantation of a VIABAHN endoprosthesis. Background The optimal treatment strategy for femoropopliteal ISR is unclear. Methods The SALVAGE study is a multicenter prospective registry involving nine US centers. Patients with femoropopliteal ISR with moderate to severe intermittent claudication or critical limb ischemia (Rutherford categories 25) and an ankle-brachial index (ABI) =0.8 were treated with excimer laser and the VIABAHN endoprosthesis. The primary efficacy endpoint is primary patency at 12 months as measured by duplex ultrasonography. The primary safety endpoint is the major adverse event (MAE) rate at 30 days. Results Twenty-seven patients were enrolled. The mean lesion length was 20.7 +/- 10.3 cm. The majority of lesions were TASC (TASC I) C and D (81.4%). All lesions were pretreated with excimer laser and percutaneous transluminal angioplasty (PTA) prior to VIABAHN implantation. Technical success was achieved in 100% of cases. There were no MAE at 30 days. Primary patency at 12 months was 48%. The ankle brachial index increased from 0.58 +/- 0.24 at baseline to 0.90 +/- 0.17 at 12 months. There was improvement in all quality-of-life parameters. The 12-month TLR rate was 17.4%. Conclusions The strategy of excimer laser atherectomy and PTA followed by implantation of a self-expanding stent graft for the treatment of femoropopliteal ISR is safe and associated with high procedural success. Primary patency rate at 12-months was suboptimal; however, the TLR rate was low. (c) 2012 Wiley Periodicals, Inc. C1 [Laird, John R., Jr.; Yeo, Khung Keong] UC Davis Med Ctr, Vasc Ctr, Sacramento, CA USA. [Rocha-Singh, Krishna] Prairie Educ & Res Cooperat, Springfield, IL USA. [Das, Tony] Cardiovasc Res Inst Dallas, Dallas, TX USA. [Joye, James] Cardiovasc Inst, Mountain View, CA USA. [Dippel, Eric] Trinity Med Ctr, Davenport, IA USA. [Reddy, Bhagat] Piedmont Hosp, Piedmont Heart Inst, Phys Grp, Atlanta, GA USA. [Botti, Charles] Riverside Methodist Hosp, Midw Res Fdn, MidOhio Cardiol & Vasc Consultants, Columbus, OH 43214 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Laird, JR (reprint author), 4860 St,Suite 3400, Sacramento, CA 95817 USA. EM john.laird@ucdmc.ucdavis.edu OI Dippel, Eric/0000-0003-1085-1178 FU W. L. Gore, Flagstaff, AZ; Spectranetics; Colorado Springs, CO; VIVA Physicians, San Jose, CA FX Grant sponsor: W. L. Gore, Flagstaff, AZ, Spectranetics, Colorado Springs, CO, and VIVA Physicians, San Jose, CA. NR 29 TC 36 Z9 37 U1 1 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 1 PY 2012 VL 80 IS 5 BP 852 EP 859 DI 10.1002/ccd.23475 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 029CL UT WOS:000310472300027 PM 22422738 ER PT J AU Hawkins, BM Drachman, DE AF Hawkins, Beau M. Drachman, Douglas E. TI Irrelevant Vessel or Ischemic Culprit? Rethinking the Importance of the Inferior Mesenteric Artery SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Drachman, Douglas E.] Massachusetts Gen Hosp, Cardiovasc Fellowship Program, Div Cardiol, Vasc Med Sect, Boston, MA 02114 USA. RP Drachman, DE (reprint author), Massachusetts Gen Hosp, Cardiovasc Fellowship Program, Div Cardiol, Vasc Med Sect, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. EM ddrachman@partners.org NR 4 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 1 PY 2012 VL 80 IS 5 BP 883 EP 884 DI 10.1002/ccd.24666 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 029CL UT WOS:000310472300033 PM 23097295 ER PT J AU Johnson, N Shapiro, GI AF Johnson, Neil Shapiro, Geoffrey I. TI Cyclin-dependent kinase 4/6 inhibition in cancer therapy SO CELL CYCLE LA English DT News Item ID CDK4/6 INHIBITION; PD 0332991; PHASE-I; SCHEDULE; ARREST C1 [Johnson, Neil] Harvard Univ, Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Johnson, N (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Inst,Med Sch, Boston, MA 02115 USA. EM geoffrey_shapiro@dfci.harvard.edu NR 9 TC 7 Z9 8 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2012 VL 11 IS 21 BP 3913 EP 3913 DI 10.4161/cc.22390 PG 1 WC Cell Biology SC Cell Biology GA 030PV UT WOS:000310583500006 PM 23032266 ER PT J AU Ho, JE Mahajan, A Chen, MH Larson, MG McCabe, EL Ghorbani, A Cheng, S Johnson, AD Lindgren, CM Kempf, T Lind, L Ingelsson, E Vasan, RS Januzzi, J Wollert, KC Morris, AP Wang, TJ AF Ho, Jennifer E. Mahajan, Anubha Chen, Ming-Huei Larson, Martin G. McCabe, Elizabeth L. Ghorbani, Anahita Cheng, Susan Johnson, Andrew D. Lindgren, Cecilia M. Kempf, Tibor Lind, Lars Ingelsson, Erik Vasan, Ramachandran S. Januzzi, James Wollert, Kai C. Morris, Andrew P. Wang, Thomas J. TI Clinical and Genetic Correlates of Growth Differentiation Factor 15 in the Community SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE CORONARY SYNDROME; MACROPHAGE INHIBITORY CYTOKINE-1; CHRONIC HEART-FAILURE; RISK STRATIFICATION; MYOCARDIAL-INFARCTION; DISEASE; PREDICTION; MARKER; ASSOCIATION; ACTIVATION AB BACKGROUND: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine produced in cardiovascular cells under conditions of inflammation and oxidative stress, is emerging as an important prognostic marker in individuals with and without existing cardiovascular disease (CVD). We therefore examined the clinical and genetic correlates of circulating GDF15 concentrations, which have not been investigated collectively. METHODS: Plasma GDF15 concentrations were measured in 2991 participants in the Framingham Offspring Study who were free of clinically overt CVD (mean age, 59 years; 56% women). Clinical correlates of GDF15 were examined in multivariable analyses. We then conducted a genomewide association study of the GDF15 concentration that included participants in the Framingham Offspring Study and participants in the PIVUS (Prospective Investigation of the Vasctilature in Uppsala Seniors) study. RESULTS: GDF15 was positively associated with age, smoking, antihypertensive treatment, diabetes, worse kidney function, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), but it was negatively associated with total cholesterol and HDL cholesterol. Clinical correlates accounted for 38% of interindividual variation in the circulating GDF15 concentration, whereas genetic factors accounted for up to 38% of the residual variability (h(2) = 0.38; P = 2.5 X 10(-11)). We identified 1 locus of genomewide significance. This locus, which is on chromosome 19p13.11 and includes the GDF15 gene, is associated with GDF15 concentration (smallest P = 2.74 X 10(-32) for rs888663). Conditional analyses revealed 2 independent association signals at this locus (rs888663 and rs1054564), which were associated with altered cis gene expression in blood cell lines. CONCLUSIONS: In ambulatory individuals, both cardio-metabolic risk factors and genetic factors play important roles in determining circulating GDF15 concentrations and contribute similarly to the overall variation. (C) 2012 American Association for Clinical Chemistry C1 [Ho, Jennifer E.; Ghorbani, Anahita; Januzzi, James; Wang, Thomas J.] Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Ho, Jennifer E.; Chen, Ming-Huei; Larson, Martin G.; Cheng, Susan; Johnson, Andrew D.; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Ho, Jennifer E.; Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Mahajan, Anubha; Lindgren, Cecilia M.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Chen, Ming-Huei; McCabe, Elizabeth L.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Dept Med, Boston, MA 02215 USA. [Cheng, Susan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. [Kempf, Tibor; Wollert, Kai C.] Hannover Med Sch, Dept Cardiol & Angiol, D-3000 Hannover, Germany. [Lind, Lars] Uppsala Univ, Dept Med, Uppsala, Sweden. [Lind, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Vasan, Ramachandran S.] Boston Univ, Dept Med, Div Cardiol & Prevent Med, Boston, MA 02215 USA. [Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, GRB-800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org RI Johnson, Andrew/G-6520-2013; OI Larson, Martin/0000-0002-9631-1254; Ho, Jennifer/0000-0002-7987-4768; Ramachandran, Vasan/0000-0001-7357-5970 FU E. Ingelsson; Swedish Research Council; Swedish Heart and Lung Foundation; Swedish Foundation for Strategic Research; Royal Swedish Academy of Sciences; Swedish Diabetes Foundation; Swedish Society of Medicine; Novo Nordisk Fonden; J. Januzzi, Roche; Siemens; BG Medicine; Thermo Fisher Scientific; K.C. Wollert; Roche Diagnostics; A.P. Morris, Wellcome Trust [WT081682, WT064890, WT090532] FX E. Ingelsson, Swedish Research Council, Swedish Heart and Lung Foundation, Swedish Foundation for Strategic Research, Royal Swedish Academy of Sciences, Swedish Diabetes Foundation, Swedish Society of Medicine, and Novo Nordisk Fonden; J. Januzzi, Roche, Siemens, BG Medicine, and Thermo Fisher Scientific; K.C. Wollert, GDF15 test kits from Roche Diagnostics; A.P. Morris, Wellcome Trust (WT081682, WT064890, and WT090532). NR 40 TC 19 Z9 21 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2012 VL 58 IS 11 BP 1582 EP 1591 DI 10.1373/clinchem.2012.190322 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 029IS UT WOS:000310489300014 PM 22997280 ER PT J AU Brunye, TT Walters, EK Ditman, T Gagnon, SA Mahoney, CR Taylor, HA AF Brunye, Tad T. Walters, Eliza K. Ditman, Tali Gagnon, Stephanie A. Mahoney, Caroline R. Taylor, Holly A. TI The Fabric of Thought: Priming Tactile Properties During Reading Influences Direct Tactile Perception SO COGNITIVE SCIENCE LA English DT Article DE Embodied cognition; Tactile imagery; Language ID LANGUAGE COMPREHENSION; SITUATION MODELS; MOTOR SYSTEM; NARRATIVE COMPREHENSION; SEMANTIC MEMORY; ACTION WORDS; REPRESENTATIONS; INFORMATION; TOUCH; TIME AB The present studies examined whether implied tactile properties during language comprehension influence subsequent direct tactile perception, and the specificity of any such effects. Participants read sentences that implicitly conveyed information regarding tactile properties (e.g., Grace tried on a pair of thick corduroy pants while shopping) that were either related or unrelated to fabrics and varied in implied texture (smooth, medium, rough). After reading each sentence, participants then performed an unrelated rating task during which they felt and rated the texture of a presented fabric. Results demonstrated that the texture properties implied in sentences influence direct tactile perception. Specifically, after reading about a smooth or rough texture, subsequent fabric ratings became notably smoother or rougher, respectively. However, we also show that there was some specificity to these effects: Fabric-related sentences elicited more specific and interactive effects on subsequent ratings. Together, we demonstrate that under certain circumstances, language comprehension can prime tactile representations and affect direct tactile perception. Results are discussed with regard to the nature and scope of multimodal mental simulation during reading. C1 [Brunye, Tad T.; Walters, Eliza K.; Ditman, Tali; Gagnon, Stephanie A.; Mahoney, Caroline R.; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Ditman, Tali] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Ditman, Tali] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Brunye, TT (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM tbrunye@alumni.tufts.edu NR 79 TC 5 Z9 5 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-0213 J9 COGNITIVE SCI JI Cogn. Sci. PD NOV-DEC PY 2012 VL 36 IS 8 BP 1449 EP 1467 DI 10.1111/j.1551-6709.2012.01268.x PG 19 WC Psychology, Experimental SC Psychology GA 030XI UT WOS:000310603000005 PM 22978497 ER PT J AU David, S Mukherjee, A Ghosh, CC Yano, M Khankin, EV Wenger, JB Karumanchi, SA Shapiro, NI Parikh, SM AF David, Sascha Mukherjee, Aditi Ghosh, Chandra C. Yano, Midori Khankin, Eliyahu V. Wenger, Julia B. Karumanchi, S. Ananth Shapiro, Nathan I. Parikh, Samir M. TI Angiopoietin-2 may contribute to multiple organ dysfunction and death in sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE angiopoietin-2; endothelium; multiple organ dysfunction; sepsis; Tie-2; vasculature ID EXCESS CIRCULATING ANGIOPOIETIN-2; TIE-2 LIGAND ANGIOPOIETIN-2; ACUTE LUNG INJURY; IN-VIVO; VASCULAR LEAKAGE; ENDOTHELIAL PERMEABILITY; AGONIST PEPTIDE; SEPTIC SHOCK; MORTALITY; ANGIOGENESIS AB Objective: In sepsis, quiescent blood vessels become leaky and inflamed by mechanisms that are incompletely understood. We hypothesized that angiopoietin-2, a partial antagonist of the endothelium-stabilizing receptor Tie-2 secreted by endothelium, contributes to adverse outcomes in this disease. Design: Laboratory and animal research. Settings: Research laboratories and Emergency Department of Beth Israel Deaconess Medical Center, Boston, MA. Subjects: Angiopoietin-2 heterozygous mice, emergency department patients. Measurements and Main Results: Mice with one functional angiopoietin-2 allele developed milder kidney and lung injury, less tissue inflammation, and less vascular leakage compared to wildtype counterparts. Heterozygotes experienced >40% absolute survival advantage following two different models of sepsis (p = .004 and .018). In human subjects presenting to our emergency department with suspected infection (n = 270 combined), circulating angiopoietin-2 was markedly elevated within the first hour of clinical care. First-hour angiopoietin-2 concentrations were proportional to current disease severity (p < .0001), rose further over time in eventual nonsurvivors (p < .0001), and predicted the future occurrence of shock (p < .0001) or death (p < .0001) in the original cohort and an independent validation group. Finally, septic human serum disrupted the barrier function of microvascular endothelial cells, an effect fully neutralized by an angiopoietin-2 monoclonal antibody. Conclusions: We conclude that angiopoietin-2 induction precedes and contributes to the adverse outcomes in sepsis, opening a new avenue for therapeutic investigation. (Crit Care Med 2012; 40: 3034-3041) C1 [David, Sascha; Mukherjee, Aditi; Ghosh, Chandra C.; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Yano, Midori; Shapiro, Nathan I.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. [David, Sascha; Mukherjee, Aditi; Ghosh, Chandra C.; Yano, Midori; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Shapiro, Nathan I.; Parikh, Samir M.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Wenger, Julia B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Parikh, SM (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. EM sparikh1@bidmc.harvard.edu RI Khankin, Eli/M-7648-2013; Shapiro, Nathan/F-1718-2016 FU NHLBI [HL091757, HL093234]; Biosile; Inverness; Cumberland; Cheetah; German Research Foundation FX Supported, in part, by funding from the NHLBI to N.I.S. (HL091757) and to S. M. P. (HL093234). Funding bodies did not have any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; Drs. Karumanchi and Parikh are listed as inventors on disclosures regarding angiopoietins filed by Beth Israel Deaconess Medical Center. Dr. Karumanchi has patents pending with Zero Dollar. Dr. Shapiro received grant support from Biosile, Inverness, Cumberland, and Cheetah. Dr. David received funding from the German Research Foundation. The remaining authors have not disclosed any potential conflicts of interest. NR 44 TC 54 Z9 56 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2012 VL 40 IS 11 BP 3034 EP 3041 DI 10.1097/CCM.0b013e31825fdc31 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 027PM UT WOS:000310365300014 PM 22890252 ER PT J AU Wilcox, SR Bittner, EA Elmer, J Seigel, TA Dhillon, A Schmidt, U AF Wilcox, Susan R. Bittner, Edward A. Elmer, Jonathan Seigel, Todd A. Dhillon, Anahat Schmidt, Ulrich TI Neuromuscular blocking agent for emergent tracheal intubation: More questions than answers Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID COMPLICATIONS C1 [Wilcox, Susan R.; Bittner, Edward A.; Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Elmer, Jonathan] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Seigel, Todd A.] Brown Univ, Rhode Isl Hosp, Dept Emergency Med, Warren Alpert Sch Med, Providence, RI 02903 USA. [Dhillon, Anahat] Univ Calif Los Angeles, Dept Anesthesia, Ronald Reagan Med Ctr, Los Angeles, CA USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2012 VL 40 IS 11 BP 3111 EP 3112 DI 10.1097/CCM.0b013e31826ab214 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 027PM UT WOS:000310365300045 ER PT J AU Wilcox, SR Bittner, EA Elmer, J Seigel, TA Dhillon, A Schmidt, U AF Wilcox, Susan R. Bittner, Edward A. Elmer, Jonathan Seigel, Todd A. Dhillon, Anahat Schmidt, Ulrich TI Not using neuromuscular blocking agents in emergent intubation should be a rarity Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID TRACHEAL INTUBATION; COMPLICATIONS; OUTCOMES C1 [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Elmer, Jonathan] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Seigel, Todd A.] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Emergency Med, Providence, RI 02903 USA. [Dhillon, Anahat] Univ Calif Los Angeles, Dept Anesthesia, Ronald Reagan Med Ctr, Los Angeles, CA USA. [Wilcox, Susan R.; Bittner, Edward A.; Schmidt, Ulrich] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2012 VL 40 IS 11 BP 3113 EP 3113 DI 10.1097/CCM.0b013e31826ab226 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 027PM UT WOS:000310365300047 ER PT J AU Jacobs, HIL van Boxtel, MPJ Gronenschild, EHBM Williams, VJ Burgmans, S Uylings, HBM Jolles, J Verhey, FRJ AF Jacobs, Heidi I. L. van Boxtel, Martin P. J. Gronenschild, Ed H. B. M. Williams, Victoria J. Burgmans, Saartje Uylings, Harry B. M. Jolles, Jelle Verhey, Frans R. J. TI Patterns of Gray and White Matter Changes in Individuals at Risk for Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Cortical thickness; diffusion tensor imaging; memory decline; Magnetic Resonance Imaging; preclinical Alzheimer's disease; early detection ID MILD COGNITIVE IMPAIRMENT; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; CORTICAL SURFACE; SPATIAL STATISTICS; COORDINATE SYSTEM; OLDER-ADULTS; ATROPHY; MRI; DEMENTIA AB Structural brain changes precede cognitive and clinical symptoms in Alzheimer's disease (AD). We aimed to examine the gray and white matter tissue changes in individuals with memory decline over a 12-year period, who might be at risk for AD. The participants were selected from the longitudinal Maastricht Aging Study based on their scores on the verbal word learning task. A group with profound memory decline over a 12-year period (n = 20) was identified and matched with a group that did not meet this criterion (n = 20). All of the participants underwent MRI scanning. Diffusion tensor imaging and cortical thickness analyses were performed to investigate the white and gray matter differences respectively. We found decreased white matter integrity in the memory decline group compared to the control group in frontal and parietal brain regions and in several cortico-cortical and cortico-subcortical tracts. Cortical thinning in the memory decline group was found in frontal, parietal, medial temporal and occipital areas. These results showed similarities with the structural brain changes observed in early AD. Thus, not only may cognitive changes be detected years before the clinical diagnosis, but typical gray and white matter changes appear to be present in older people with memory decline as well. This suggests that a combination of cognitive decline and structural brain changes might be an ideal biomarker for AD pathogenesis. C1 [Jacobs, Heidi I. L.; van Boxtel, Martin P. J.; Gronenschild, Ed H. B. M.; Burgmans, Saartje; Uylings, Harry B. M.; Jolles, Jelle; Verhey, Frans R. J.] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, NL-6200 MD Maastricht, Netherlands. [Jacobs, Heidi I. L.; van Boxtel, Martin P. J.; Gronenschild, Ed H. B. M.; Burgmans, Saartje; Uylings, Harry B. M.; Jolles, Jelle; Verhey, Frans R. J.] European Grad Sch Neurosci EURON, NL-6200 MD Maastricht, Netherlands. [Jacobs, Heidi I. L.] Res Ctr Julich, Inst Neurosci & Med 3, Cognit Neurol Sect, D-52425 Julich, Germany. [Williams, Victoria J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Uylings, Harry B. M.] Vrije Univ Amsterdam Med Ctr, Dept Anat & Neurosci, NL-1007 MB Amsterdam, Netherlands. [Jolles, Jelle] Vrije Univ Amsterdam, Fac Psychol & Educ, AZIRE Res Inst, Amsterdam, Netherlands. RP Jacobs, HIL (reprint author), Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Alzheimer Ctr Limburg, POB 616, NL-6200 MD Maastricht, Netherlands. EM h.jacobs@maastrichtuniversity.nl RI Jacobs, Heidi/E-9550-2011 OI Jacobs, Heidi/0000-0001-7620-3822 FU FP6 EU program Marie Curie Actions [MEST-CT-2005-020589] FX The design and conduction of this study were supported by a grant obtained from the FP6 EU program Marie Curie Actions [MEST-CT-2005-020589]. NR 65 TC 3 Z9 3 U1 1 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD NOV PY 2012 VL 9 IS 9 BP 1097 EP 1105 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 028RZ UT WOS:000310441500009 PM 22920268 ER PT J AU Depta, JP Bhatt, DL AF Depta, Jeremiah P. Bhatt, Deepak L. TI Antiplatelet therapy and proton pump inhibition: cause for concern? SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE antiplatelet; aspirin; clopidogrel; CYP450; platelet function ID PERCUTANEOUS CORONARY INTERVENTION; PATIENTS RECEIVING CLOPIDOGREL; ADVERSE CARDIOVASCULAR EVENTS; TREATMENT PLATELET REACTIVITY; MYOCARDIAL-INFARCTION; CONCOMITANT USE; ARTERY-DISEASE; ADENOSINE-DIPHOSPHATE; STENT IMPLANTATION; DRUG-INTERACTION AB Purpose of review To review the current evidence on the clinical significance of the drug-drug interactions between the available antiplatelet agents and proton pump inhibitors (PPIs). Recent findings Gastrointestinal bleeding is associated with higher rates of morbidity and mortality following a myocardial infarction. PPIs are commonly used to prevent gastrointestinal bleeding. PPIs can attenuate metabolism of clopidogrel to its active metabolite by inhibiting various hepatic CYP450 enzymes, mainly CYP2C19. Concomitant use of a PPI with clopidogrel reduces clopidogrel active metabolite generation and subsequent platelet inhibition. In observational studies, the clinical significance of this drug-drug interaction is mixed. Evidence from the only randomized trial studying the clinical implications of the PPI-clopidogrel interaction did not demonstrate any difference in cardiovascular outcomes but did show a reduction in gastrointestinal bleeding with use of a PPI. Summary The drug-drug interaction between antiplatelet agents and PPIs at the enzymatic level does not seem to result in worse clinical outcomes. The risk of gastrointestinal bleeding with antiplatelet therapy is substantial. Clinicians should use PPIs in selected high-risk patients to prevent gastrointestinal bleeding. C1 [Bhatt, Deepak L.] VA Boston Healthcare Syst, TIMI Study Grp, Boston, MA 02132 USA. [Depta, Jeremiah P.] Washington Univ, Sch Med, Dept Med, Div Cardiol, St Louis, MO USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Integrated Intervent Cardiovasc Program, Boston, MA 02115 USA. RP Bhatt, DL (reprint author), VA Boston Healthcare Syst, TIMI Study Grp, 1400 VFW Pkwy, Boston, MA 02132 USA. EM Dlbhattmd@post.harvard.edu FU Amarin; AstraZeneca; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; Sanofi Aventis; The Medicines Company FX Disclosures: D. L. B. discloses the following relationships - Advisory Board: Medscape Cardiology; Board of Directors: Boston VA Research Institute, Society of Chest Pain Centers; Chair: American Heart Association Get With The Guidelines Science Subcommittee; Honoraria: American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), WebMD (CME steering committees); Research Grants: Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; Unfunded Research: FlowCo, PLx Pharma, Takeda. He had served as the Chair of the COGENT trial (unfunded). NR 67 TC 16 Z9 16 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2012 VL 27 IS 6 BP 642 EP 650 DI 10.1097/HCO.0b013e32835830b6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 027ON UT WOS:000310362600012 PM 23075823 ER PT J AU DeBeradinis, B Januzzi, JL AF DeBeradinis, Benedetta Januzzi, James L., Jr. TI Use of biomarkers to guide outpatient therapy of heart failure SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE B-type natriuretic peptide/B-type natriuretic peptide and its amino-terminal equivalent; heart failure; outcomes ID BRAIN-NATRIURETIC PEPTIDE; CARDIAC-RESYNCHRONIZATION THERAPY; MANAGEMENT; MORTALITY; IMPROVE; PROBNP; BNP; DIAGNOSIS; TRIAL; CARE AB Purpose of review Among patients with heart failure, concentrations of natriuretic peptides are strongly linked to the presence and severity of structural heart disease and are strongly prognostic in this setting. Additionally, favorable reduction in the concentration of either B-type natriuretic peptide (BNP) or B-type natriuretic peptide and its amino-terminal cleavage fragment (NT-proBNP) may be seen during treatment of heart failure, with parallel improvement in prognosis. This has led to the hypothesis that intensified treatment directed at reducing natriuretic peptide concentrations may improve outcomes in heart failure. Recent findings In chronic heart failure, studies suggest that a strategy of standard-of-care management together with a goal to suppress BNP or NT-proBNP concentrations leads to greater application of guideline-derived medical therapy and is well tolerated. In certain studies of this BNP or NT-proBNP 'guided' approach, patients treated with biomarker-guided care had superior outcomes when compared with standard heart failure management alone, particularly in younger study populations, in patients with left ventricular systolic dysfunction, and particularly when substantial reductions in natriuretic peptides were achieved in association with biomarker-guided care. Summary Natriuretic peptide 'guided' management appears promising in patients suffering from chronic heart failure. Large-scale pivotal trials to confirm the approach are planned. C1 [DeBeradinis, Benedetta; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org FU Roche Diagnostics; Critical Diagnostics; Siemens; Thermo-Fisher FX Dr Januzzi: Grant support from Roche Diagnostics, Critical Diagnostics, Siemens, and Thermo-Fisher. Dr DeBeradinis has no conflicts of interest. NR 35 TC 11 Z9 11 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2012 VL 27 IS 6 BP 661 EP 668 DI 10.1097/HCO.0b013e3283587c4d PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 027ON UT WOS:000310362600015 PM 22941124 ER PT J AU Quraishi, SA Camargo, CA AF Quraishi, Sadeq A. Camargo, Carlos A., Jr. TI Vitamin D in acute stress and critical illness SO CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE LA English DT Review DE 25(OH)D; acute illness; critical care; vitamin D ID SERUM 25-HYDROXYVITAMIN D; RESPIRATORY-TRACT INFECTION; C-REACTIVE PROTEIN; NUTRITION EXAMINATION SURVEY; ACUTE MYOCARDIAL-INFARCTION; INTENSIVE-CARE-UNIT; YOUNG FINNISH MEN; D DEFICIENCY; D SUPPLEMENTATION; PARATHYROID-HORMONE AB Purpose of review The pleotropic effects of vitamin D on chronic diseases have received significant attention; however, its role in acute illness is less understood. The purpose of this review is to summarize the current evidence regarding the role of vitamin D in acute stress and critical illness. Recent findings 25-Hydroxyvitamin D levels may affect risk of developing acute illnesses (e.g. respiratory infections), and low concentrations are associated with unfavorable outcomes during critical care. Inflammatory changes alone do not explain the observed deterioration in vitamin D status following acute stress. Hemodilution, interstitial extravasation, decreased synthesis of binding proteins, and renal wasting of 25-hydroxyvitamin D, all appear to play a more significant role in the regulation of vitamin D status during critical illness. Summary Single-point assessments of 25-hydroxyvitamin D following acute stress may provide an inaccurate assessment of vitamin D status. In such cases, measurement of binding proteins and free vitamin D metabolites may be essential to create a more realistic approximation of vitamin D status. Variations in patient responses to acute stress and critical illness may depend not only on the degree of systemic vitamin D insufficiency, but also on the individual tissue requirements. C1 [Quraishi, Sadeq A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Quraishi, SA (reprint author), Harvard Univ, Sch Med, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. EM squraishi@partners.org FU National Institutes of Health (NIH) [5T32GM007592-33, UL1 RR025758]; NIH [R01 AI093723, U01 AI087881] FX Dr Quraishi received support from the National Institutes of Health (NIH) grants 5T32GM007592-33 (Harvard Anaesthesia Center) and UL1 RR025758 (Harvard Scholars in Clinical Science Program). He also serves on the Board of Directors of the Vitamin D Council; whereas Dr Camargo received support from NIH grants R01 AI093723 and U01 AI087881. NR 85 TC 29 Z9 31 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1363-1950 J9 CURR OPIN CLIN NUTR JI Curr. Opin. Clin. Nutr. Metab. Care PD NOV PY 2012 VL 15 IS 6 BP 625 EP 634 DI 10.1097/MCO.0b013e328358fc2b PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 027OI UT WOS:000310362000015 PM 23075939 ER PT J AU Castelino, FV AF Castelino, Flavia V. TI Lipids and eicosanoids in fibrosis: emerging targets for therapy SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE eicosanoids; lysophospholipids; pulmonary fibrosis; systemic sclerosis ID INDUCED PULMONARY-FIBROSIS; LYSOPHOSPHATIDIC ACID PRODUCTION; BRONCHOALVEOLAR LAVAGE FLUID; SCLERODERMA LUNG-DISEASE; PROSTAGLANDIN-E SYNTHASE; SPHINGOSINE 1-PHOSPHATE; DIHYDROSPHINGOSINE 1-PHOSPHATE; PROSTANOID RECEPTORS; SYSTEMIC-SCLEROSIS; LEUKOTRIENE B-4 AB Purpose of review Lipid mediators including the lysophospholipids, sphingolipids and eicosanoids have long been implicated in inflammation, cancer and numerous other diseases. Over the last decade, new research suggests a role for these mediators in fibrosis. Recent findings Recent developments in the study of fibrotic mediators have centered on lysophospholipids and eicosanoids. New research is evaluating metabolic-profiling strategies to quantitatively measure lipid mediators in human plasma. Lysophosphatidic acid receptor antagonists are currently under development with early phase trials scheduled for idiopathic pulmonary fibrosis and scleroderma dermal fibrosis. Eicosanoids have long been implicated in maintaining tissue homeostasis, and the balance of profibrotic and antifibrotic effects has drawn attention in recent years. Targeting the prostanoids, specifically PGE(2) and PGI(2), as well as the leukotrienes is now being considered for antifibrotic therapies. Summary Lipid mediators have significant roles in many disease processes. Significant research now suggests a critical role for these mediators in the pathogenesis of fibrosis. Targeting these mediators is a promising area of drug discovery. C1 Massachusetts Gen Hosp, Div Rheumatol, Boston, MA 02114 USA. RP Castelino, FV (reprint author), Massachusetts Gen Hosp, Div Rheumatol, Yawkey 2C-2100,55 Fruit St, Boston, MA 02114 USA. EM fcastelino@partners.org FU National Institute of Arthritis and Musculoskeletal and Skin Diseases [K08AR062592]; Scleroderma Foundation FX F.V.C does not have any conflicts of interest. F.V.C. is supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR062592) and the Scleroderma Foundation. NR 58 TC 6 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI Curr. Opin. Rheumatol. PD NOV PY 2012 VL 24 IS 6 BP 649 EP 655 DI 10.1097/BOR.0b013e328356d9f6 PG 7 WC Rheumatology SC Rheumatology GA 016US UT WOS:000309545600010 PM 22810365 ER PT J AU Koreth, J AF Koreth, John TI INTERLEUKIN-2 AND REGULATORY T-CELLS IN GRAFT-VERSUS-HOST DISEASE SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 12th Euroconference on Clinical Cell Analysis in conjuction with its 8th European Clinical Cytometry Course CY SEP 11-15, 2012 CL Budapest, HUNGARY SP European Soc Clin Cell Anal (ESCCA) C1 [Koreth, John] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2012 VL 82B IS 6 BP 378 EP 379 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 027XB UT WOS:000310386300019 ER PT J AU Chuang, GS Manstein, D Tannous, Z Avram, MM AF Chuang, Gary S. Manstein, Dieter Tannous, Zeina Avram, Mathew M. TI Ulceration of Mature Surgical Scars Following Nonablative Fractional Photothermolysis Associated with Intralesional Lidocaine Injections SO DERMATOLOGIC SURGERY LA English DT Editorial Material ID LOCAL-ANESTHETICS; ENHANCEMENT C1 [Chuang, Gary S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr,Dept Dermatol, Boston, MA 02114 USA. RP Chuang, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser & Cosmet Ctr,Dept Dermatol, 50 Staniford St, Boston, MA 02114 USA. EM gary.s.chuang@gmail.com NR 7 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 2012 VL 38 IS 11 BP 1879 EP 1881 DI 10.1111/j.1524-4725.2012.02576.x PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 030EB UT WOS:000310550800020 PM 22973818 ER PT J AU Herr, A Longworth, M Ji, JY Korenjak, M MacAlpine, DM Dyson, NJ AF Herr, Anabel Longworth, Michelle Ji, Jun-Yuan Korenjak, Michael MacAlpine, David M. Dyson, Nicholas J. TI Identification of E2F target genes that are rate limiting for dE2F1-dependent cell proliferation SO DEVELOPMENTAL DYNAMICS LA English DT Article DE E2F; ORC; PCNA; Drosophila ID ORIGIN RECOGNITION COMPLEX; DNA-REPLICATION; S-PHASE; TRANSCRIPTION FACTOR; CYCLE PROGRESSION; MICROARRAY ANALYSIS; CDT1 DEGRADATION; DROSOPHILA; EXPRESSION; DESTRUCTION AB Background: Microarray studies have shown that the E2F transcription factor influences the expression of many genes but it is unclear how many of these targets are important for E2F-mediated control of cell proliferation. Results: We assembled a collection of mutant alleles of 44 dE2F1-dependent genes and tested whether these could modify visible phenotypes caused by the tissue-specific depletion of dE2F1. More than half of the mutant alleles dominantly enhanced de2f1-dsRNA phenotypes suggesting that the in vivo functions of dE2F1 can be limited by the reduction in the level of expression of many different targets. Unexpectedly, several mutant alleles suppressed de2f1-dsRNA phenotypes. One of the strongest of these suppressors was Orc5. Depletion of ORC5 increased proliferation in cells with reduced dE2F1 and specifically elevated the expression of dE2F1-regulated genes. Importantly, these effects were independent of dE2F1 protein levels, suggesting that reducing the level of ORC5 did not interfere with the general targeting of dE2F1. Conclusions: We propose that the interaction between ORC5 and dE2F1 may reflect a feedback mechanism between replication initiation proteins and dE2F1 that ensures that proliferating cells maintain a robust level of replication proteins for the next cell cycle. Developmental Dynamics 241:16951707, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Herr, Anabel; Longworth, Michelle; Ji, Jun-Yuan; Korenjak, Michael; Dyson, Nicholas J.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Herr, Anabel; Longworth, Michelle; Ji, Jun-Yuan; Korenjak, Michael; Dyson, Nicholas J.] Harvard Univ, Sch Med, Mol Oncol Lab, Charlestown, MA 02129 USA. [MacAlpine, David M.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Ctr Canc, 13th St,Bldg 149,MC149-7330, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NIH [HG004279, CA64402, GM53203]; Charles A. King Trust; MGH FX Grant sponsor: NIH; Grant numbers: HG004279, CA64402, and GM53203.; We thank Terry Orr-Weaver and Bob Duronio for dE2F1 antibodies, Manfred Gossen for the OCR5 antibody, Bob Duronio for the PCNA-GFP transgenic line used in this study and for sharing unpublished data. We also thank the members of the Dyson Laboratory for advice and technical assistance. M. S. L. was supported by a Fellowship Award from the Charles A. King Trust and J.J. was supported in part by a Tosteson Postdoctoral Fellowship from the MGH. This study was supported by NIH grant HG004279 to D.M.M. and NIH grants CA64402 and GM53203 to N.D. NR 58 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2012 VL 241 IS 11 BP 1695 EP 1707 DI 10.1002/dvdy.23857 PG 13 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 026NF UT WOS:000310285300005 PM 22972499 ER PT J AU George, JT Seminara, SB AF George, Jyothis T. Seminara, Stephanie B. TI Kisspeptin and the Hypothalamic Control of Reproduction: Lessons from the Human SO ENDOCRINOLOGY LA English DT Review ID GONADOTROPIN-RELEASING-HORMONE; PITUITARY-GONADAL AXIS; KISS1 GENE-EXPRESSION; MONKEY MACACA-MULATTA; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; RHESUS-MONKEY; HYPOGONADOTROPIC HYPOGONADISM; HUMAN METASTIN-45-54; SEXUAL-DIMORPHISM AB The hypothalamic hormone GnRH is a central driver of pituitary gonadotropin secretion, controlling pulsatile gonadotropin secretion, modulating gonadal steroid feedback, and bringing about full fertility in the adult. Thus, understanding GnRH neuronal regulation is essential to understanding the neurohumoral control of human reproduction. Genetic tools were used in patients with GnRH deficiency (i.e. idiopathic hypogonadotropic hypogonadism), a clinical syndrome that results from the failure of a normal pattern of pulsatile GnRH, to discover upstream modulators of GnRH secretion (1). In 2003, homozygosity mapping of two consanguineous pedigrees led to the identification of loss of function mutations in KISS1R (a G protein coupled receptor) by two groups (2, 3). In parallel, the Kiss1r(-/-) mouse was shown to be a phenocopy of the human GnRH-deficient state, demonstrating that the function of KISS1R/Kiss1r is conserved across mammalian species (4). Just before these human genetic discoveries, the ligand for kisspeptin-1 receptor [KISS1R; also known as G protein coupled receptor 54 (GPR54)], was discovered to be kisspeptin. Soon thereafter a large array of experimental studies began assembling genetic, expression, physiologic, transgenic, knockdown, and electrophysiological data to characterize the physiology of kisspeptin and its seminal role in modulating GnRH release. (Endocrinology 153: 5130-5136, 2012) C1 [Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Reprod Endocrine Unit, Boston, MA 02114 USA. [George, Jyothis T.] Univ Edinburgh, Med Res Council Ctr Reprod Hlth, Edinburgh EH16 4TJ, Midlothian, Scotland. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, Reprod Endocrine Unit, 55 Fruit St,Bartlett Hall Extens 5, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu OI George, Jyothis/0000-0002-5299-775X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research [U54HD028138]; Medical Research Council [G0701682]; Novo Nordisk UK Research Foundation; Excellence in Diabetes Research Awards; Scottish Clinical Research Excellence Development Scheme (SCREDS); [R01 HD043341]; [K24 HD067388] FX S.B.S. and some of the data referenced in this article were supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development/National Institutes of Health through Cooperative Agreement U54HD028138 as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research as well as Grants R01 HD043341 and K24 HD067388. J.T.G.'s work has been funded by the Medical Research Council (G0701682) with additional support from the Novo Nordisk UK Research Foundation and the Excellence in Diabetes Research Awards. His current position is funded by the Scottish Clinical Research Excellence Development Scheme (SCREDS). NR 58 TC 22 Z9 23 U1 2 U2 23 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2012 VL 153 IS 11 BP 5130 EP 5136 DI 10.1210/en.2012-1429 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027NL UT WOS:000310359300003 PM 23015291 ER PT J AU Katsuta, H Aguayo-Mazzucato, C Katsuta, R Akashi, T Hollister-Lock, J Sharma, AJ Bonner-Weir, S Weir, GC AF Katsuta, Hitoshi Aguayo-Mazzucato, Cristina Katsuta, Rimiko Akashi, Tomoyuki Hollister-Lock, Jennifer Sharma, Arun J. Bonner-Weir, Susan Weir, Gordon C. TI Subpopulations of GFP-Marked Mouse Pancreatic beta-Cells Differ in Size, Granularity, and Insulin Secretion SO ENDOCRINOLOGY LA English DT Article ID B-CELLS; GLUCOSE; HETEROGENEITY; ISLETS; RAT; STIMULATION AB There is growing information about the heterogeneity of pancreatic beta-cells and how it relates to insulin secretion. This study used the approach of flow cytometry to sort and analyze beta-cells from transgenic mice expressing green fluorescent protein (GFP) under the control of the mouse insulin I gene promoter. Three populations of beta-cells with differing GFP brightness could be identified, which were classified as GFP-low, GFP-medium, and GFP-bright. The GFP-medium population comprised about 70% of the total. The GFP-low population had less insulin secretion as determined by the reverse hemolytic plaque assay and reduced insulin gene expression. Additionally, all three subpopulations of beta-cells were found in mice of varying ages (embryonic d 15.5 and postnatal wk 1-9). The three populations from the youngest had larger cells (forward scatter) and less granularity (side scatter) than those from the adults. This approach opens up new ways to advance knowledge about beta-cell heterogeneity. (Endocrinology 153: 5180-5187, 2012) C1 [Katsuta, Hitoshi; Aguayo-Mazzucato, Cristina; Katsuta, Rimiko; Akashi, Tomoyuki; Hollister-Lock, Jennifer; Sharma, Arun J.; Bonner-Weir, Susan; Weir, Gordon C.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div,Dept Med, Boston, MA 02215 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol,Res Div,Dept Med, 1 Joslin Pl, Boston, MA 02215 USA. EM gordon.weir@joslin.harvard.edu FU Juvenile Diabetes Research Foundation; National Institutes of Health [RO1-DK66056]; Flow Cytometry and Advanced Microscopy Cores of Joslin Diabetes and Endocrinology Research Center [P30 DK36836]; Diabetes Research and Wellness Foundation FX This study was supported by the Juvenile Diabetes Research Foundation, the National Institutes of Health (RO1-DK66056), the Flow Cytometry and Advanced Microscopy Cores of Joslin Diabetes and Endocrinology Research Center (P30 DK36836), and the Diabetes Research and Wellness Foundation. NR 28 TC 11 Z9 11 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2012 VL 153 IS 11 BP 5180 EP 5187 DI 10.1210/en.2012-1257 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 027NL UT WOS:000310359300009 PM 22919061 ER PT J AU Makinodan, E Marneros, AG AF Makinodan, Eri Marneros, Alexander G. TI Protein kinase A activation inhibits oncogenic Sonic hedgehog signalling and suppresses basal cell carcinoma of the skin SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE basal cell carcinoma; forskolin; protein kinase A ID HUMAN HOMOLOG; PATHWAY INHIBITOR; SHH PATHWAY; MEDULLOBLASTOMA; MUTATIONS; GLI2; TUMORIGENESIS; DEGRADATION; PROTECTION; GROWTH AB Basal cell carcinoma of the skin (BCC) is caused by constitutive activation of the Sonic hedgehog (Shh) pathway, mainly through mutations either in the Shh receptor Patched (PTCH) or in its co-receptor Smoothened (Smo). Inhibitors of this pathway that are currently in clinical trials inhibit Smo. However, mutations in Smo can result in resistance to these inhibitors. To target most BCCs and avoid acquired resistance because of Smo mutations, inhibiting the Shh-pathway downstream of Smo is critical. Attractive downstream targets would be at the level of Gli proteins, the transcriptional activators of this pathway in BCCs. Previously it has been shown that Gli1 and Gli2, when phosphorylated by protein kinase A (PKA), are targeted for proteosomal degradation. Here we show that PKA activation via the cAMP agonist forskolin is sufficient to completely abolish oncogenic Smo activity in vitro. In an inducible BCC mouse model due to a Smo mutation that confers resistance to current Smo inhibitors, topical forskolin treatment significantly reduced Gli1 mRNA levels and resulted in strongly suppressed BCC tumor growth. Our data show that forskolin inhibits the growth of even those BCCs that are resistant to Smo inhibitors and provide a proof-of-principle framework for the development of topically applied human skin-permeable novel pharmacologic inhibitors of oncogenic Shh-signaling through PKA activation. C1 [Makinodan, Eri; Marneros, Alexander G.] Harvard Univ, Dept Dermatol, Sch Med, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Marneros, AG (reprint author), Harvard Univ, Dept Dermatol, Sch Med, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, CNY 149,Rm 3-216,13th St, Charlestown, MA 02129 USA. EM amarneros@partners.org NR 31 TC 10 Z9 12 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2012 VL 21 IS 11 BP 847 EP 852 DI 10.1111/exd.12016 PG 6 WC Dermatology SC Dermatology GA 025TN UT WOS:000310217600007 PM 23163650 ER PT J AU Colaci, DS Afeiche, M Gaskins, AJ Wright, DL Toth, TL Tanrikut, C Hauser, R Chavarro, JE AF Colaci, Daniela S. Afeiche, Myriam Gaskins, Audrey J. Wright, Diane L. Toth, Thomas L. Tanrikut, Cigdem Hauser, Russ Chavarro, Jorge E. TI Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article DE Body mass index; men's obesity; IVF; ICSI ID ASSISTED REPRODUCTIVE TECHNOLOGY; LIVE BIRTH-RATES; OBESE MEN; SEMEN QUALITY; HORMONE-LEVELS; SPERM; WOMEN; INFERTILITY; AGE; OVERWEIGHT AB Objective: To evaluate the association between men's body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). Design: Prospective cohort study. Setting: Fertility clinic in an academic medical center. Patient(s): 114 couples who underwent 172 assisted reproduction cycles. Intervention(s): None. Main Outcome Measure(s): Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. Result(s): The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men's BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men's BMI was unrelated to positive beta-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84% lower than the odds in couples with men with normal BMI. Conclusion(s): Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection. (Fertil Steril (R) 2012;98:1193-9. (C) 2012 by American Society for Reproductive Medicine.) C1 [Colaci, Daniela S.; Afeiche, Myriam; Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Tanrikut, Cigdem] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Wright, Diane L.; Toth, Thomas L.; Tanrikut, Cigdem; Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hauser, Russ; Chavarro, Jorge E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Colaci, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM dcolaci@hsph.harvard.edu FU NIEHS [ES009718, ES000002]; NIDDK [DK46200] FX Supported by grants ES009718 and ES000002 from the NIEHS, and DK46200 from NIDDK. NR 34 TC 29 Z9 30 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2012 VL 98 IS 5 BP 1193 EP + DI 10.1016/j.fertnstert.2012.07.1102 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 028TW UT WOS:000310447300027 PM 22884013 ER PT J AU Desbordes, G Negi, LT Pace, TWW Wallace, BA Raison, CL Schwartz, EL AF Desbordes, Gaelle Negi, Lobsang T. Pace, Thaddeus W. W. Wallace, B. Alan Raison, Charles L. Schwartz, Eric L. TI Effects of mindful-attention and compassion meditation training on amygdala response to emotional stimuli in an ordinary, non-meditative state SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE meditation; mindfulness; attention; compassion; amygdala; emotion; fMRI ID LOVING-KINDNESS MEDITATION; STRESS REDUCTION; INDIVIDUAL-DIFFERENCES; GENDER-DIFFERENCES; GRAY-MATTER; QUANTITATIVE METAANALYSIS; FUNCTIONAL NEUROANATOMY; AFFECTIVE NEUROSCIENCE; BEHAVIORAL-RESPONSES; PSYCHOSOCIAL STRESS AB The amygdala has been repeatedly implicated in emotional processing of both positive and negative-valence stimuli. Previous studies suggest that the amygdala response to emotional stimuli is lower when the subject is in a meditative state of mindful-attention, both in beginner meditators after an 8-week meditation intervention and in expert meditators. However, the longitudinal effects of meditation training on amygdala responses have not been reported when participants are in an ordinary, non-meditative state. In this study, we investigated how 8 weeks of training in meditation affects amygdala responses to emotional stimuli in subjects when in a non-meditative state. Healthy adults with no prior meditation experience took part in 8 weeks of either Mindful Attention Training (MAT), Cognitively-Based Compassion Training (CBCT; a program based on Tibetan Buddhist compassion meditation practices), or an active control intervention. Before and after the intervention, participants underwent an fMRI experiment during which they were presented images with positive, negative, and neutral emotional valences from the IAPS database while remaining in an ordinary, non-meditative state. Using a region-of-interest analysis, we found a longitudinal decrease in right amygdala activation in the Mindful Attention group in response to positive images, and in response to images of all valences overall. In the CBCT group, we found a trend increase in right amygdala response to negative images, which was significantly correlated with a decrease in depression score. No effects or trends were observed in the control group. This finding suggests that the effects of meditation training on emotional processing might transfer to non-meditative states. This is consistent with the hypothesis that meditation training may induce learning that is not stimulus- or task-specific, but process-specific, and thereby may result in enduring changes in mental function. C1 [Desbordes, Gaelle] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Desbordes, Gaelle; Schwartz, Eric L.] Boston Univ, Ctr Computat Neurosci & Neural Technol, Boston, MA 02215 USA. [Negi, Lobsang T.] Emory Univ, Dept Relig, Atlanta, GA 30322 USA. [Pace, Thaddeus W. W.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Wallace, B. Alan] Santa Barbara Inst Consciousness Studies, Santa Barbara, CA USA. [Raison, Charles L.] Univ Arizona, Coll Med, Dept Psychiat, Tucson, AZ USA. [Raison, Charles L.] Univ Arizona, Coll Agr, Norton Sch Family & Consumer Sci, Tucson, AZ 85721 USA. [Schwartz, Eric L.] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Desbordes, G (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Boston, MA 02129 USA. EM desbordes@gmail.com FU National Institutes of Health National Center for Complementary and Alternative Medicine [R01AT004698, R01AT004698-01A1S1, ARRA RC1AT005728] FX This study was funded by the National Institutes of Health National Center for Complementary and Alternative Medicine (R01AT004698 and R01AT004698-01A1S1, P.I. Raison; ARRA RC1AT005728, P.I. Schwartz). The authors thank Bruce Rosen, Willa Miller, Sara Lazar, and Britta Holzel for helpful discussions, Jonathan Polimeni, Thomas Benner, and Vitaly Napadow for help with the fMRI experimental design, Doug Greve and Jonathan Polimeni for helpful suggestions regarding data analysis, Teri Sivilli for valuable help with study coordination, and meditation instructors Brendan Ozawa- de Silva, Brooke Dodson-Lavelle, Tom Comstock, and Bryan Price for providing the training to the study participants in the CBCT and MAT groups. NR 141 TC 65 Z9 66 U1 25 U2 136 PU FRONTIERS RES FOUND PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD NOV 1 PY 2012 VL 6 AR 292 DI 10.3389/fnhum.2012.00292 PG 15 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 030KJ UT WOS:000310569300001 PM 23125828 ER PT J AU Halder, I Mehdi, H Singh, M Gutman, R Barrington, E Aleong, R Bloom, H Dudley, S Ellinor, PT Saba, S Shalaaby, A Weiss, R London, B AF Halder, Indrani Mehdi, Haider Singh, Madhurmeet Gutman, Rebecca Barrington, Elisabeth Aleong, Ryan Bloom, Heather Dudley, Samuel Ellinor, Patrick T. Saba, Samir Shalaaby, Alaa Weiss, Raul London, Barry TI Race-dependent Associations Between Variations in ADRB1 and Ventricular Arrhythmias SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Halder, Indrani; Mehdi, Haider; Singh, Madhurmeet; Gutman, Rebecca; Barrington, Elisabeth; Saba, Samir; Shalaaby, Alaa; London, Barry] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Aleong, Ryan] Univ Colorado, Boulder, CO 80309 USA. [Bloom, Heather] Emory Univ, Atlanta, GA 30322 USA. [Dudley, Samuel] Univ Illinois, Chicago, IL USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiss, Raul] Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 28 BP 728 EP 728 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200034 ER PT J AU Sebro, R Peloso, G Dupuis, J Risch, N AF Sebro, Ronnie Peloso, Gina Dupuis, Josee Risch, Neil TI Random Mating - Fact or Fiction? Evidence for Multigenerational Non-random Mating SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Sebro, Ronnie; Risch, Neil] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. [Peloso, Gina] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 31 BP 728 EP 729 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200037 ER PT J AU Manning, AK Sim, X Locke, AE Agarwala, V Moutsianas, L Weyant, R McCarthy, MI Altshuler, D Boehnke, M AF Manning, Alisa K. Sim, Xueling Locke, Adam E. Agarwala, Vineeta Moutsianas, Loukas Weyant, Robert McCarthy, Mark I. Altshuler, David Boehnke, Michael TI Comparing Power for Gene-based and Low-frequency SNP Tests in Quantitative Traits (a GoT2D Study) SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Manning, Alisa K.; Agarwala, Vineeta] Broad Inst Harvard & MIT, Cambridge, MA USA. [Manning, Alisa K.; Altshuler, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sim, Xueling; Locke, Adam E.; Weyant, Robert; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Agarwala, Vineeta; Altshuler, David] Harvard Univ, Sch Med, Boston, MA USA. [Moutsianas, Loukas] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [McCarthy, Mark I.] Churchill Hosp, Oxford OX3 7LJ, England. [McCarthy, Mark I.] Wellcome Trust Ctr Human Genet Res, Oxford, England. [Altshuler, David] Broad Inst, Cambridge, MA USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 144 BP 761 EP 761 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200149 ER PT J AU Hiraki, LT Joshi, A Lindstrom, S Chan, AT Chanock, S Kraft, P AF Hiraki, Linda T. Joshi, Amit Lindstrom, Sara Chan, Andrew T. Chanock, Stephen Kraft, Peter TI Building and Assessing Protein-Protein Interaction Networks from Genome Wide Association Results in Cancer SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Hiraki, Linda T.; Joshi, Amit; Lindstrom, Sara; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chanock, Stephen] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 178 BP 771 EP 771 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200183 ER PT J AU Chen, H Meigs, JB Dupuis, J AF Chen, Han Meigs, James B. Dupuis, Josee TI Sequence Kernel Association Test in Family Data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES) CY OCT 18-20, 2012 CL Stevenson, WA SP Int Genet Epidemiol Soc (IGES) C1 [Chen, Han; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Meigs, James B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Cambridge, MA 02138 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Dupuis, Josee] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2012 VL 36 IS 7 MA 181 BP 772 EP 772 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 021VJ UT WOS:000309913200186 ER PT J AU Tomson, TT Kapa, S Bala, R Riley, MP Lin, D Epstein, AE Deo, R Dixit, S AF Tomson, Todd T. Kapa, Suraj Bala, Rupa Riley, Michael P. Lin, David Epstein, Andrew E. Deo, Rajat Dixit, Sanjay TI Risk of stroke and atrial fibrillation after radiofrequency catheter ablation of typical atrial flutter SO HEART RHYTHM LA English DT Article DE Ablation; Catheter ablation; Atrial flutter; Atrial fibrillation; Stroke; Thromboembolism ID TERM-FOLLOW-UP; CAVOTRICUSPID ISTHMUS; CLINICAL-COURSE; COMMON; ARRHYTHMIAS; PREDICTORS AB BACKGROUND Studies suggest that 18%-50% of the patients develop atrial fibrillation (AF) after typical atrial flutter (AFL) ablation. However, little data exist about the incidence of and risk factors for stroke and AF after successful ablation of typical AFL. OBJECTIVES To determine the risk of stroke and AF after radio-frequency ablation of typical AFL. METHODS A retrospective review of patients undergoing AFL ablation between 2002 and 2010 was performed to determine the incidence of and risk factors for stroke and AF after successful ablation of typical AFL. RESULTS The study cohort consisted of 126 patients (age 66 +/- 10 years) with a mean follow-up of 40 +/- 30 months after ablation. Following successful AFL ablation, AF occurred in 46 patients (37%), with an incidence of 104 cases of documented AF per 1000 person-years after AFL ablation. Twenty patients (16%) developed new AF after AFL ablation. Stroke occurred in 8 patients (6%) during follow-up, with an incidence of 21 strokes per 1000 person-years. Six of the 8 patients (75%) with strokes had documented AF occurrences after AFL ablation. The presence of AF after AFL ablation was the only risk factor associated with the risk for future stroke. CONCLUSIONS Patients with typical AFL undergoing successful ablation are at an elevated risk for AF and stroke following the procedure. Because postprocedure AF is the only identifiable risk factor for stroke, rigorous monitoring of patients after typical AFL may help identify those patients who are at an increased risk for stroke. C1 [Dixit, Sanjay] Hosp Univ Penn, Sect Cardiac Electrophysiol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Dixit, S (reprint author), Hosp Univ Penn, Sect Cardiac Electrophysiol, 9 Founders Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM sanjay.dixit@uphs.upenn.edu NR 20 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2012 VL 9 IS 11 BP 1779 EP 1784 DI 10.1016/j.hrthm.2012.07.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 029XY UT WOS:000310532300009 PM 22813577 ER PT J AU Lo Re, V Volk, J Newcomb, CW Yang, YX Freeman, CP Hennessy, S Kostman, JR Tebas, P Leonard, MB Localio, AR AF Lo Re, Vincent, III Volk, Jessica Newcomb, Craig W. Yang, Yu-Xiao Freeman, Cristin P. Hennessy, Sean Kostman, Jay R. Tebas, Pablo Leonard, Mary B. Localio, A. Russell TI Risk of hip fracture associated with hepatitis c virus infection and hepatitis C/human immunodeficiency virus coinfection SO HEPATOLOGY LA English DT Article ID BONE-MINERAL DENSITY; ANTIRETROVIRAL THERAPY; VIRAL CIRRHOSIS; PROPENSITY SCORE; UNITED-STATES; LIVER-DISEASE; PREVALENCE; ALPHA; OSTEOPOROSIS; VETERANS AB Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our aims were to determine whether persons with HCV infection alone are at increased risk for hip fracture, compared to uninfected individuals, and to examine whether the risk of hip fracture is higher among HCV/HIV-coinfected persons, compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV-coinfected, 276,901 HCV-monoinfected, 95,827 HIV-monoinfected, and 3,110,904 HCV/HIV-uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999-2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1,000 person-years), increased with the presence of either HIV infection (1.95 events/1,000 person-years) or HCV infection (2.69 events/1,000 person-years), and were highest among HCV/HIV-coinfected individuals (3.06 events/1,000 person-years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip fracture, compared to HCV-monoinfected (HR, 1.38; 95% CI: 1.25-1.53), HIV-monoinfected (females: HR, 1.76; 95% CI: 1.44-2.16; males: HR, 1.36; 95% CI: 1.20-1.55), and HCV/HIV-uninfected persons (females: HR, 2.65; 95% CI: 2.21-3.17; males: HR, 2.20; 95% CI: 1.97-2.47). HCV monoinfection was associated with an increased risk of hip fracture, compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18-39 years: HR, 3.56; 95% CI: 2.93-4.32; males, 18-39 years: HR, 2.40; 95% CI: 2.02-2.84). Conclusion: Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture, compared to HCV-monoinfected, HIV-monoinfected, and HCV/HIV-uninfected persons. HCV-monoinfected patients had an increased risk of hip fracture, compared to uninfected individuals. (HEPATOLOGY 2012;56:16881698) C1 [Lo Re, Vincent, III; Kostman, Jay R.; Tebas, Pablo] Univ Penn, Div Infect Dis, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Newcomb, Craig W.; Yang, Yu-Xiao; Freeman, Cristin P.; Hennessy, Sean; Leonard, Mary B.; Localio, A. Russell] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Volk, Jessica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Yang, Yu-Xiao] Univ Penn, Div Gastroenterol, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Leonard, Mary B.] Univ Penn, Div Nephrol, Dept Pediat, Childrens Hosp Philadelphia,Perelman Sch Med, Philadelphia, PA 19104 USA. RP Lo Re, V (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, Sch Med, 836 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015 FU National Institute of Allergy and Infectious Diseases [K01-AI070001, U01-AI069467]; National Institute of Diabetes and Digestive and Kidney Diseases [K24-DK076808]; National Institutes of Health [UL1-RR024134]; Penn FOCUS Medical Student Fellowship in Women's Health (Bertha Dagan Berman Award) FX This study was supported by the National Institute of Allergy and Infectious Diseases (research grants K01-AI070001 and U01-AI069467), the National Institute of Diabetes and Digestive and Kidney Diseases (research grant K24-DK076808), the Clinical and Translational Science Award from the National Institutes of Health (grant no.: UL1-RR024134), and a Penn FOCUS Medical Student Fellowship in Women's Health (Bertha Dagan Berman Award). NR 44 TC 37 Z9 37 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 1688 EP 1698 DI 10.1002/hep.25866 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100014 PM 22619086 ER PT J AU Srivastava, J Siddiq, A Emdad, L Santhekadur, PK Chen, D Gredler, R Shen, XN Robertson, CL Dumur, CI Hylemon, PB Mukhopadhyay, ND Bhere, D Shah, K Ahmad, R Giashuddin, S Stafflinger, J Subler, MA Windle, JJ Fisher, PB Sarkar, D AF Srivastava, Jyoti Siddiq, Ayesha Emdad, Luni Santhekadur, Prasanna Kumar Chen, Dong Gredler, Rachel Shen, Xue-Ning Robertson, Chadia L. Dumur, Catherine I. Hylemon, Phillip B. Mukhopadhyay, Nitai D. Bhere, Deepak Shah, Khalid Ahmad, Rushdy Giashuddin, Shah Stafflinger, Jillian Subler, Mark A. Windle, Jolene J. Fisher, Paul B. Sarkar, Devanand TI Astrocyte elevated gene-1 promotes hepatocarcinogenesis: Novel insights from a mouse model SO HEPATOLOGY LA English DT Article ID HEPATOCELLULAR-CARCINOMA; C-MYC; ANGIOGENESIS; METASTASIS; LIVER; AEG-1; CHEMORESISTANCE; ACTIVATION; EXPRESSION; ONCOGENE AB Astrocyte elevated gene-1 (AEG-1) is a key contributor to hepatocellular carcinoma (HCC) development and progression. To enhance our understanding of the role of AEG-1 in hepatocarcinogenesis, a transgenic mouse with hepatocyte-specific expression of AEG-1 (Alb/AEG1) was developed. Treating Alb/AEG-1, but not wild-type (WT) mice, with N-nitrosodiethylamine resulted in multinodular HCC with steatotic features and associated modulation of expression of genes regulating invasion, metastasis, angiogenesis, and fatty acid synthesis. Hepatocytes isolated from Alb/AEG-1 mice displayed profound resistance to chemotherapeutics and growth factor deprivation with activation of prosurvival signaling pathways. Alb/AEG-1 hepatocytes also exhibited marked resistance toward senescence, which correlated with abrogation of activation of a DNA damage response. Conditioned media from Alb/AEG-1 hepatocytes induced marked angiogenesis with elevation in several coagulation factors. Among these factors, AEG-1 facilitated the association of factor XII (FXII) messenger RNA with polysomes, resulting in increased translation. Short interfering RNAmediated knockdown of FXII resulted in profound inhibition of AEG-1-induced angiogenesis. Conclusion: We uncovered novel aspects of AEG-1 functions, including induction of steatosis, inhibition of senescence, and activation of the coagulation pathway to augment aggressive hepatocarcinogenesis. The Alb/AEG-1 mouse provides an appropriate model to scrutinize the molecular mechanism of hepatocarcinogenesis and to evaluate the efficacy of novel therapeutic strategies targeting HCC. (HEPATOLOGY 2012;56:17821791) C1 [Windle, Jolene J.; Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Sch Med, Inst Mol Med, Richmond, VA 23298 USA. [Srivastava, Jyoti; Siddiq, Ayesha; Emdad, Luni; Santhekadur, Prasanna Kumar; Gredler, Rachel; Shen, Xue-Ning; Robertson, Chadia L.; Stafflinger, Jillian; Subler, Mark A.; Windle, Jolene J.; Fisher, Paul B.; Sarkar, Devanand] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Human & Mol Genet, Boston, MA USA. [Chen, Dong; Dumur, Catherine I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Hylemon, Phillip B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Microbiol & Immunol, Boston, MA USA. [Mukhopadhyay, Nitai D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. [Bhere, Deepak; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neuropathy & Imaging Lab,Dept Radiol, Boston, MA USA. [Bhere, Deepak; Shah, Khalid] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neuropathy & Imaging Lab,Dept Neurol, Boston, MA USA. [Ahmad, Rushdy] Broad Inst Harvard & Massachusetts Inst Technol, Prote Grp, Boston, MA USA. [Giashuddin, Shah] New York Hosp Med Ctr, Dept Pathol, Flushing, NY USA. [Dumur, Catherine I.; Hylemon, Phillip B.; Windle, Jolene J.; Fisher, Paul B.; Sarkar, Devanand] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. RP Sarkar, D (reprint author), Virginia Commonwealth Univ, Sch Med, Inst Mol Med, 1220 E Broad St,POB 980035, Richmond, VA 23298 USA. EM dsarkar@vcu.edu RI SRIVASTAVA, JYOTI/J-6065-2014; OI SRIVASTAVA, JYOTI/0000-0002-5727-741X; Windle, Jolene/0000-0001-6690-385X FU James S. McDonnell Foundation; National Cancer Institute [R01 CA138540]; Samuel Waxman Cancer Research Foundation (SWCRF); National Institutes of Health [R01 CA134721] FX The present study was supported, in part, by grants from the James S. McDonnell Foundation and National Cancer Institute (grant no.: R01 CA138540; to D. S.), the Samuel Waxman Cancer Research Foundation (SWCRF; grant to D. S. and P. B. F.), and the National Institutes of Health (grant no.: R01 CA134721; to P. B. F.). D. S. is the Harrison Endowed Scholar in Cancer Research and a Blick scholar. P. B. F. holds the Thelma Newmeyer Corman Chair in Cancer Research and is a SWCRF investigator. NR 27 TC 37 Z9 41 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2012 VL 56 IS 5 BP 1782 EP 1791 DI 10.1002/hep.25868 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030BR UT WOS:000310543100023 PM 22689379 ER PT J AU Doyle, LA Nelson, D Heinrich, MC Corless, CL Hornick, JL AF Doyle, Leona A. Nelson, Dylan Heinrich, Michael C. Corless, Christopher L. Hornick, Jason L. TI Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: a comprehensive genotype-phenotype correlation study SO HISTOPATHOLOGY LA English DT Article DE gastrointestinal stromal tumour; KIT; PDGFRA; soft tissue sarcoma; succinate dehydrogenase ID CARNEY-STRATAKIS-SYNDROME; OF-FUNCTION MUTATIONS; V600E BRAF MUTATIONS; TERM-FOLLOW-UP; FAMILIAL PHEOCHROMOCYTOMA; PULMONARY CHONDROMA; GERMLINE MUTATIONS; MOLECULAR-GENETICS; PARAGANGLIOMA; TRIAD AB Aims: Gastrointestinal stromal tumours (GISTs) typically harbour KIT or PDGFRA mutations; 15% of adult GISTs and >90% in children lack such mutations ('wild-type' GISTs). Paediatric and occasional adult GISTs show similar, distinctive features: multinodular architecture and epithelioid morphology, indolent behaviour with metastases, and imatinib resistance. Recent studies have suggested that these tumours can be identified by loss of succinate dehydrogenase subunit B (SDHB) expression. The aim of this study was to validate the predictive value of SDHB immunohistochemistry in a large genotyped cohort. Methods and results: SDHB expression was examined in GISTs with known genotypes: 179 with KIT mutations, 32 with PDGFRA mutations, and 53 wild type. Histological features were recorded without knowledge of genotype or SDHB status. SDHB was deficient in 22 (42%) wild-type GISTs. All other tumours showed intact SDHB expression. All SDHB-deficient GISTs with known primary sites arose in the stomach, and had multinodular architecture and epithelioid or mixed morphology. None of the wildtype GISTs with intact SDHB showed multinodular architecture, and only four (13%) had epithelioid morphology. Conclusions: SDHB-deficient GISTs are wild-type gastric tumours with distinctive histology. Immunohistochemistry for SDHB can be used to confirm the diagnosis of this tumour class. SDHB expression is retained in all GISTs with KIT and PDGFRA mutations. C1 [Doyle, Leona A.; Hornick, Jason L.] Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Nelson, Dylan; Corless, Christopher L.] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA. [Nelson, Dylan; Heinrich, Michael C.; Corless, Christopher L.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland VA Med Ctr, Portland, OR 97201 USA. RP Hornick, JL (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM jhornick@partners.org FU Department of Veterans Affairs; Life Raft Group; GIST Cancer Research Fund FX This work was supported in part by a Merit Review Grant from the Department of Veterans Affairs (M. C. Heinrich), and funding from the Life Raft Group (M. C. Heinrich and C. L. Corless) and the GIST Cancer Research Fund (M. C. Heinrich and C. L. Corless). NR 42 TC 34 Z9 38 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD NOV PY 2012 VL 61 IS 5 BP 801 EP 809 DI 10.1111/j.1365-2559.2012.04300.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 029GI UT WOS:000310482400007 PM 22804613 ER PT J AU Mehta, DD Zanartu, M Feng, SW Cheyne, HA Hillman, RE AF Mehta, Daryush D. Zanartu, Matias Feng, Shengran W. Cheyne, Harold A., II Hillman, Robert E. TI Mobile Voice Health Monitoring Using a Wearable Accelerometer Sensor and a Smartphone Platform SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Accelerometer sensor; vocal hyperfunction; voice production model; voice use; wearable voice sensor ID ACCUMULATOR; SPEECH; VIBRATION; TEACHERS; SYSTEM; MODEL AB Many common voice disorders are chronic or recurring conditions that are likely to result from faulty and/or abusive patterns of vocal behavior, referred to generically as vocal hyperfunction. An ongoing goal in clinical voice assessment is the development and use of noninvasively derived measures to quantify and track the daily status of vocal hyperfunction so that the diagnosis and treatment of such behaviorally based voice disorders can be improved. This paper reports on the development of a new, versatile, and cost-effective clinical tool for mobile voice monitoring that acquires the high-bandwidth signal from an accelerometer sensor placed on the neck skin above the collarbone. Using a smartphone as the data acquisition platform, the prototype device provides a user-friendly interface for voice use monitoring, daily sensor calibration, and periodic alert capabilities. Pilot data are reported from three vocally normal speakers and three subjects with voice disorders to demonstrate the potential of the device to yield standard measures of fundamental frequency and sound pressure level and model-based glottal airflow properties. The smartphone-based platform enables future clinical studies for the identification of the best set of measures for differentiating between normal and hyperfunctional patterns of voice use. C1 [Mehta, Daryush D.; Feng, Shengran W.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. [Mehta, Daryush D.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Mehta, Daryush D.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Mehta, Daryush D.] Univ Melbourne, Dept Otolaryngol, Parkville, Vic 3010, Australia. [Zanartu, Matias] Univ Tecn Federico Santa Maria, Dept Elect Engn, Valparaiso 1680, Chile. [Feng, Shengran W.] MIT, Speech & Hearing Biosci & Technol Program, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Cheyne, Harold A., II] Cornell Univ, Ornithol Lab, Bioacoust Res Program, Ithaca, NY 14853 USA. [Hillman, Robert E.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. EM daryush.mehta@alum.mit.edu; matias.zanartu@usm.cl; willfeng@mit.edu; hac68@cornell.edu; hillman.robert@mgh.harvard.edu RI Zanartu, Matias/I-3133-2012; Emchi, Karma/Q-1952-2016 OI Zanartu, Matias/0000-0001-5581-4392; FU National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders [R21 DC011588, T32 DC00038]; Institute of Laryngology and Voice Restoration; Chilean CONICYT [FONDECYT 11110147] FX This work was supported by the National Institutes of Health (NIH) National Institute on Deafness and Other Communication Disorders under Grant R21 DC011588 and Grant T32 DC00038, by the Institute of Laryngology and Voice Restoration, and by the Chilean CONICYT under Grant FONDECYT 11110147. Asterisk indicates corresponding author. NR 28 TC 36 Z9 36 U1 0 U2 24 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 2012 VL 59 IS 11 BP 3090 EP 3096 DI 10.1109/TBME.2012.2207896 PG 7 WC Engineering, Biomedical SC Engineering GA 025AM UT WOS:000310154700012 PM 22875236 ER PT J AU Jacobs, PG Silaski, G Wilmington, D Gordon, S Helt, W McMillan, G Fausti, SA Dille, M AF Jacobs, Peter G. Silaski, Grayson Wilmington, Debra Gordon, Samuel Helt, Wendy McMillan, Garnett Fausti, Stephen A. Dille, Marilyn TI Development and Evaluation of a Portable Audiometer for High-Frequency Screening of Hearing Loss From Ototoxicity in Homes/Clinics SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Hearing screening; high-frequency (HF) audiometry; ototoxicity monitoring ID PRODUCT OTOACOUSTIC EMISSIONS AB Cancer treatment often requires patients to be exposed to drugs that can damage hearing. Drugs such as cisplatin can cause permanent damage to hearing if not detected early. Damage typically occurs first in the more basal regions of the cochlea which are specific for high-frequency (HF) hearing and progresses to more apical regions that are relevant to speech understanding. Monitoring of HF hearing loss can be an effective means for early detection of ototoxicity caused by chemotherapy. Once ototoxicity is detected, the oncology medical team could adjust the drug dosage or switch to medications that are less ototoxic. Telehealth technology may improve access to ototoxicity monitoring. Patients could monitor their own hearing using a device that alerts healthcare professionals in the event of a change in hearing. A portable audiometer is currently not available that is 1) capable of automatic or manual (by an audiologist) operation; 2) designed with precision pure-tone functionality up to 20 kHz; and 3) able to remotely transfer health status information to a healthcare professional. This paper describes the design of a technology, the ototoxicity identification (OtoID), that includes a portable audiometer with HF test functionality that meets ANSI/ASA S3.6-2010 standards and is capable of reliably detecting a person's drug-related hearing changes relative to a baseline period (i.e., before ototoxic drugs) using an automated test. The system includes a wireless cellular modem capable of notifying a remote healthcare professional in the event that a significant change in hearing has occurred in the patient. The system was evaluated on test subjects within a sound-proof booth, a noisy hospital ward, and within their homes. Results indicate that the OtoID system can be used by patients to effectively monitor hearing changes remotely within their home or in a hospital ward, ultimately enabling early detection of ototoxicity and potentially avoiding hearing loss. C1 [Jacobs, Peter G.; Wilmington, Debra; Gordon, Samuel; Helt, Wendy; McMillan, Garnett; Fausti, Stephen A.; Dille, Marilyn] Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. [Silaski, Grayson] GRAYSON SILASKI, Portland, OR 97221 USA. RP Jacobs, PG (reprint author), Portland VA Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR 97239 USA. EM peter.jacobs@va.gov; ncc621@gmail.com; debwilm@comcast.net; samuel.gordon@va.gov; Wendy.Helt@va.gov; garnett.mcmillan@va.gov; sa.fausti@frontier.com; marilyn.dille@va.gov FU U.S. Department of Veterans Affairs [C6373R] FX This work was supported in part by the U.S. Department of Veterans Affairs under Grant C6373R. Asterisk indicates corresponding author. NR 14 TC 6 Z9 6 U1 0 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 2012 VL 59 IS 11 BP 3097 EP 3103 DI 10.1109/TBME.2012.2204881 PG 7 WC Engineering, Biomedical SC Engineering GA 025AM UT WOS:000310154700013 PM 22801480 ER PT J AU Rodgers, RF Franko, DL Brunet, A Herbert, CF Bui, E AF Rodgers, Rachel F. Franko, Debra L. Brunet, Alain Herbert, Christophe F. Bui, Eric TI Disordered eating following exposure to television and internet coverage of the March 2011 japan earthquake SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE media; disaster coverage; disordered eating; internet ID VICARIOUS TRAUMATIZATION; STRESS; SYMPTOMS; ATTACKS; TRAUMA; PTSD; RISK AB Objective: To prospectively explore the relationship between exposure to potentially distressing news content and disordered eating. Method: Within 2 weeks of the March 3, 2011 Japan earthquake, an online survey was conducted among non-Japanese adults in distant countries (N = 698) assessing time spent on TV and the internet watching the news as well as peritraumatic reactions to the news and sleep disturbance. Participants were invited to complete a followup survey two months later [n = 113, mean age (SD) = 38.8 (11.91), 73% female] reporting on eating disorder symptoms. Results: Exposure to TV and, to a lesser extent, internet coverage of the Japan disaster were associated with disordered eating, in particular dieting and oral control, as measured by the eating attitudes test. Peritraumatic reactions and sleep disturbance displayed specific patterns of association with disordered eating. Discussion: Exposure to media coverage of distant disasters may be associated with increased disordered eating. (C) 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012;45:845849) C1 [Rodgers, Rachel F.] Univ Toulouse 2, Ctr Etude & Rech Psychopathol, Toulouse, France. [Rodgers, Rachel F.; Franko, Debra L.] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. [Rodgers, Rachel F.; Bui, Eric] Univ Toulouse, Lab Stress Traumat, Toulouse, France. [Rodgers, Rachel F.; Bui, Eric] CHU Toulouse, Toulouse, France. [Brunet, Alain; Herbert, Christophe F.] McGill Univ, Montreal, PQ, Canada. [Brunet, Alain; Herbert, Christophe F.] Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Rodgers, RF (reprint author), Univ Toulouse 2, Ctr Etude & Rech Psychopathol, Toulouse, France. EM rodgers.rachel@gmail.com RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 FU Toulouse University Hospital; Association Traumapsy; Fonds de la Recherche en Sante du Quebec FX Supported by Toulouse University Hospital, Association Traumapsy, and Fonds de la Recherche en Sante du Quebec. NR 17 TC 1 Z9 1 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2012 VL 45 IS 7 BP 845 EP 849 DI 10.1002/eat.22031 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 026JG UT WOS:000310271600004 PM 22693016 ER PT J AU Nelson, BD Ahn, R Fehling, M Eckardt, MJ Conn, KL El-Bashir, A Tiernan, M Purcell, G Burke, TF AF Nelson, Brett D. Ahn, Roy Fehling, Maya Eckardt, Melody J. Conn, Kathryn L. El-Bashir, Alaa Tiernan, Margaret Purcell, Genevieve Burke, Thomas F. TI Evaluation of a novel training package among frontline maternal, newborn, and child health workers in South Sudan SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Child health; Maternal health; Midwifery; Newborn health; South Sudan; Traditional birth attendant; Training package ID DEVELOPING-COUNTRIES; BIRTH ATTENDANTS; MORTALITY AB Objective: To develop, implement, and evaluate an evidence-based Maternal, Newborn, and Child Survival (MNCS) package for frontline health workers (FHWs) in South Sudan. Methods: A multimodal needs assessment was conducted to develop a best-evidence package comprised of targeted training, pictorial checklists, and reusable equipment and commodities. Implementation utilized a training-of-trainers model. Program effectiveness was assessed through knowledge assessments. objective structured clinical examinations (OSCEs), focus groups, and questionnaires. Results: A total of 72 trainers and 708 FHWs were trained in 7 South Sudan states. Trainer knowledge assessments improved significantly: from 62.7% to 92.0% (P<0.001). Mean FHW scores on maternal OSCEs were 21.1% pre-training, 83.4% post-training, and 61.5% 2-3 months after training (P<0.001). Corresponding mean newborn OSCE scores were 41.6%, 89.8%, and 45.7% (P<0.001). Questionnaires revealed high levels of use, satisfaction, and confidence. FHWs reported an average of 3.0 referrals (range, 0-20) to healthcare facilities during the 2-3 months following training, and 78.3% of FHWs were more likely to refer patients. Seven focus groups showed high satisfaction with trainings, commodities, and checklists, with few barriers. Conclusion: The MNCS package has led to improved FHW knowledge, skills, and referral. A novel package of training, checklists, and equipment can be successfully implemented in resource-limited settings and enhance links between community-based providers and healthcare facilities. (C) 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Nelson, Brett D.; Ahn, Roy; Fehling, Maya; Eckardt, Melody J.; Conn, Kathryn L.; El-Bashir, Alaa; Tiernan, Margaret; Purcell, Genevieve; Burke, Thomas F.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Boston, MA 02114 USA. [Nelson, Brett D.; Ahn, Roy; Burke, Thomas F.] Harvard Univ, Sch Med, Boston, MA USA. [Nelson, Brett D.; Burke, Thomas F.] Massachusetts Gen Hosp, Div Global Hlth, Dept Pediat, Boston, MA 02114 USA. [Eckardt, Melody J.] Boston Med Ctr, Boston, MA USA. [Fehling, Maya; El-Bashir, Alaa; Tiernan, Margaret] Maternal Newborn & Child Survival Initiat, Juba, South Sudan, Sudan. [Burke, Thomas F.] Childrens Hosp Boston, Boston, MA USA. RP Nelson, BD (reprint author), Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Dept Emergency Med, Zero Emerson Pl, Boston, MA 02114 USA. EM brett.d.nelson@gmail.com OI Eckardt, Melody/0000-0001-9066-9856; Nelson, Brett/0000-0002-5049-1798 FU Ministry of Health of the Republic of South Sudan; Multi-Donor Trust Fund for South Sudan FX Funding for this initiative came from the Ministry of Health of the Republic of South Sudan and from the Multi-Donor Trust Fund for South Sudan. NR 22 TC 6 Z9 6 U1 0 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD NOV PY 2012 VL 119 IS 2 BP 130 EP 135 DI 10.1016/j.ijgo.2012.05.019 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 021OR UT WOS:000309895700007 PM 22944212 ER PT J AU Hatano, H Scherzer, R Wu, Y Harvill, K Maka, K Hoh, R Sinclair, E Palmer, S Martin, JN Busch, MP Deeks, SG Hsue, PY AF Hatano, Hiroyu Scherzer, Rebecca Wu, Yuaner Harvill, Kara Maka, Kristinalisa Hoh, Rebecca Sinclair, Elizabeth Palmer, Sarah Martin, Jeffrey N. Busch, Michael P. Deeks, Steven G. Hsue, Priscilla Y. TI A Randomized Controlled Trial Assessing the Effects of Raltegravir Intensification on Endothelial Function in Treated HIV Infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; raltegravir intensification; endothelial function; flow-mediated vasodilation ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL-ACTIVATION; SUPPRESSIVE ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION RATES; FLOW-MEDIATED VASODILATION; POLYMERASE-CHAIN-REACTION; BRACHIAL-ARTERY; CARDIOVASCULAR-DISEASE; RISK-FACTOR; INDIVIDUALS AB Objectives: To determine whether intensification with raltegravir improves endothelial function in antiretroviral-treated HIV-infected individuals. Design: Randomized, double-blinded, placebo-controlled study. Methods: Fifty-six subjects with treatment-mediated viral suppression for at least 1 year were randomized to add 400 mg of raltegravir twice daily or matching placebo for 24 weeks. The primary endpoint was the difference in rate of change in endothelial function [as assessed by flow-mediated vasodilation (FMD) of the brachial artery] from baseline to week 24 between the raltegravir and placebo groups. Linear mixed models were used to evaluate the association of treatment group with changes in FMD, immune activation, and measures of viral persistence. Results: At baseline, the median CD4(+) T-cell count was 498 cells/mm(3), nadir CD4(+) T-cell count was 191 cells/mm(3), duration of HIV infection was 18 years, FMD was 3.3%, and hyperemic velocity (a marker of microvascular function) was 68.3 cm. There were no significant differences between treatment groups in rate of change in FMD (raltegravir group: +0.032% per week, placebo group: +0.023% per week; P = 0.60). There were also no differences between treatment groups in rate of change in hyperemic velocity, immune activation, or viral persistence. In multivariable analysis, older age, longer duration of HIV infection, and current abacavir use were associated with lower FMD. Lower CD4(+) T-cell count and current abacavir use were associated with lower hyperemic velocity. Conclusions: The addition of raltegravir to suppressive antiretroviral therapy did not have a significant impact on cardiovascular risk, as assessed by endothelial function (ClinicalTrials.gov NCT00843713). C1 [Hatano, Hiroyu; Scherzer, Rebecca; Wu, Yuaner; Harvill, Kara; Maka, Kristinalisa; Hoh, Rebecca; Sinclair, Elizabeth; Deeks, Steven G.; Hsue, Priscilla Y.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Scherzer, Rebecca] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Palmer, Sarah] Karolinska Inst, Solna, Sweden. [Palmer, Sarah] Swedish Inst Infect Dis Control, Solna, Sweden. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Busch, Michael P.] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA. RP Hatano, H (reprint author), San Francisco Gen Hosp, Bldg 80,Ward 84,995 Potrero Ave, San Francisco, CA 94110 USA. EM hhatano@php.ucsf.edu FU National Institutes of Health [K23AI075985, K24AI069994, AI052745, AI055273, RR 16482, R01 HL095130, R01 AI087145, R01 AI057020]; American Foundation for AIDS Research [106710-40-RGRL, 107170-44-RGRL]; University of California; San Francisco/Gladstone Institute of Virology and Immunology Center for AIDS Research (CFAR) [P30 AI027763]; University of California, San Francisco Clinical and Translational Research Institute Clinical Research Center [UL1 RR024131]; Center for AIDS Prevention Studies [P30 MH62246]; Center for HIV/AIDS Vaccine Immunology [U01 AI067854]; CFAR Network of Integrated Systems Grant [R24 AI067039]; Merck, Inc. FX Supported by National Institutes of Health Grant K23AI075985, K24AI069994, AI052745, AI055273, RR 16482, R01 HL095130, R01 AI087145, and R01 AI057020; American Foundation for AIDS Research Grants 106710-40-RGRL and 107170-44-RGRL; the University of California, San Francisco/Gladstone Institute of Virology and Immunology Center for AIDS Research (CFAR) Grant P30 AI027763; the University of California, San Francisco Clinical and Translational Research Institute Clinical Research Center Grant UL1 RR024131; the Center for AIDS Prevention Studies Grant P30 MH62246; the Center for HIV/AIDS Vaccine Immunology Grant U01 AI067854; and the CFAR Network of Integrated Systems Grant R24 AI067039.; H. Hatano and S. G. Deeks have received research support from Merck, Inc. Study drug provided by Merck at no cost for this study. The other authors have no conflicts of interest to disclose. NR 47 TC 19 Z9 19 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2012 VL 61 IS 3 BP 317 EP 325 DI 10.1097/QAI.0b013e31826e7d0f PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029TR UT WOS:000310519300014 PM 22918156 ER PT J AU Noubary, F Hughes, MD AF Noubary, Farzad Hughes, Michael D. TI Factors Affecting Timing of Antiretroviral Treatment Initiation Based on Monitoring CD4 Counts SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; CD4(+) T-lymphocyte; patient management; method agreement; flow cytometry ID HIV-INFECTED PATIENTS; MULTICENTER AIDS COHORT; CELL COUNT; NAIVE PATIENTS; CARE; ENUMERATION; LYMPHOCYTE; THERAPY; DECLINE AB Objective: To evaluate factors affecting antiretroviral therapy (ART) start time when triggered by a CD4 count <350 cells/mu L while monitoring counts over time. Measurement frequency, requirement for confirmatory counts, and precision and accuracy of CD4 enumeration technology were considered. Methods: Using a model of CD4 count trajectories among seroconverters in the Multicenter AIDS Cohort Study, sequences of counts were simulated for a large hypothetical population monitored for 5 years from seroconversion. Time of first count <350 cells/mu L was defined as ART start time. The simulation was adapted to evaluate the effect of the above factors on these times. ART initiation was considered "very late" among patients whose underlying trajectory declined less than 200 cells/mL during the period simulated if no previous observed count was <350 cells/mu L. Results: For 12-, 6-, 4-, and 3-monthly measurements, median start time was 48, 36, 32, and 30 months after seroconversion and proportion of patients starting ART very late was 11.5%, 1.6%, 0.2%, and 0.1%. For 6-monthly measurements, requiring confirmation increased the median to 49 months and proportion to 8.9%. Changes in standard deviation of short-term variability in counts of 25% and measurement bias for a novel technology of +/- 10% changed median time by +/- 6 months with modest change in the proportion very late (range, 0.5%-3.2%). Conclusion: 6-monthly measurements appear adequate in achieving low rates of very late ART whereas confirmation affects rates adversely. Studies comparing new versus standard measurement technologies should focus on ruling out modest bias, particularly proximal to important thresholds for treatment management. C1 [Noubary, Farzad; Hughes, Michael D.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Noubary, Farzad] Massachusetts Gen Hosp, Dept Gen Med, Boston, MA 02114 USA. RP Noubary, F (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM fnoubary@partners.org FU United States National Institutes of Health [AI 24643, AI 68634, AI 42006, AI 60354] FX Supported in part by United States National Institutes of Health Grants AI 24643, AI 68634, AI 42006, and AI 60354. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. NR 30 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2012 VL 61 IS 3 BP 326 EP 333 DI 10.1097/QAI.0b013e31826be75e PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029TR UT WOS:000310519300015 PM 22878419 ER PT J AU Tien, PC Schneider, MF Cox, C Karim, R Cohen, M Sharma, A Young, M Glesby, MJ AF Tien, Phyllis C. Schneider, Michael F. Cox, Christopher Karim, Roksana Cohen, Mardge Sharma, Anjali Young, Mary Glesby, Marshall J. TI Association of HIV Infection With Incident Diabetes Mellitus: Impact of Using Hemoglobin A1C as a Criterion for Diabetes SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE diabetes mellitus; HIV; women; hemoglobin A1C ID WOMENS INTERAGENCY HIV; ANTIRETROVIRAL THERAPY EXPOSURE; MULTICENTER AIDS COHORT; GLYCATED HEMOGLOBIN; INSULIN-RESISTANCE; RISK; ATHEROSCLEROSIS AB Background: Data regarding the association between HIV and diabetes mellitus (DM) are conflicting, with little known regarding the impact of including hemoglobin A1C (A1C) as a criterion for DM. Methods: Pooled logistic regression was used to quantify the association between HIV and DM in 1501 HIV-infected and 550 HIV-uninfected participants from the Women's Interagency HIV Study. Incident DM was defined using the following 3 criteria, definition I: fasting glucose (FG) >= 126 mg/dL, anti-DM medication or reporting DM diagnosis (with confirmation by FG >= 126 mg/dL or anti-DM medication); definition II: confirmation with a second FG >= 126 mg/dL, and definition III: addition of A1C >= 6.5% confirmed by FG >= 126 mg/dL or anti-DM medication. Results: DM incidence per 100 person-years was 2.44, 1.55, and 1.70 for HIV-infected women; 1.89, 0.85, and 1.13 for HIV-uninfected women, using definition I, II, and III, respectively. After adjustment for traditional DM risk factors, HIV infection was associated with 1.23-, 1.90-, and 1.38-fold higher risk of incident DM, respectively; the association reached statistical significance only when confirmation with a second FG >= 126 mg/dL was required. Older age, obesity, and a family history of DM were each consistently and strongly associated with increased DM risk. Conclusions: HIV infection is consistently associated with greater risk of DM. Inclusion of an elevated A1C to define DM increases the accuracy of the diagnosis and only slightly attenuates the magnitude of the association otherwise observed between HIV and DM. By contrast, a DM diagnosis made without any confirmatory criteria for FG >= 126 mg/dL overestimates the incidence, while also underestimating the effects of HIV on DM risk, and should be avoided. C1 [Tien, Phyllis C.] Univ Calif San Francisco, Vet Adm Med Ctr, Infect Dis Sect, Dept Med, San Francisco, CA 94121 USA. [Tien, Phyllis C.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schneider, Michael F.; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Karim, Roksana] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Cohen, Mardge] Stroger Hosp, Dept Med, Chicago, IL USA. [Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA. [Sharma, Anjali] Suny Downstate Med Ctr, Dept Med, Brooklyn, NY USA. [Young, Mary] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Glesby, Marshall J.] Weill Cornell Med Coll, Dept Med, New York, NY USA. RP Tien, PC (reprint author), Univ Calif San Francisco, Vet Adm Med Ctr, Infect Dis Sect, Dept Med, 111W,4150 Clement St, San Francisco, CA 94121 USA. EM ptien@ucsf.edu FU National Institute of Allergy and Infectious Diseases [U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, U01-AI-42590, R01 AI087176, K24 AI078884]; Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant [U01-HD-32632]; National Cancer Institute, National Institute on Drug Abuse, and National Institute on Deafness and Other Communication Disorders; National Center for Research Resources (UCSF-CTSI) [UL1 RR024131] FX Supported by the National Institute of Allergy and Infectious Diseases Grants U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590; Eunice Kennedy Shriver National Institute of Child Health and Human Development Grant U01-HD-32632. The study is cofunded by the National Cancer Institute, National Institute on Drug Abuse, and National Institute on Deafness and Other Communication Disorders.; Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). Drs. Tien and Glesby are supported by the National Institute of Allergy and Infectious Diseases through R01 AI087176 and K24 AI078884, respectively. NR 23 TC 17 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2012 VL 61 IS 3 BP 334 EP 340 DI 10.1097/QAI.0b013e31826bfc32 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029TR UT WOS:000310519300016 PM 22878421 ER PT J AU Hwang, JJ Wei, J Abbara, S Grinspoon, SK Lo, J AF Hwang, Janice J. Wei, Jeffrey Abbara, Suhny Grinspoon, Steven K. Lo, Janet TI Receptor Activator of Nuclear Factor-kappa B Ligand (RANKL) and Its Relationship to Coronary Atherosclerosis in HIV Patients SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE atherosclerosis; receptor activator of nuclear factor kappa beta ligand; osteoprotegerin; coronary artery disease; HIV ID ACUTE MYOCARDIAL-INFARCTION; OSTEOPROTEGERIN LEVELS; SERUM-LEVELS; EXPRESSION; BONE; OSTEOCLASTOGENESIS; DISEASE; MEN; CALCIFICATION; PLAQUE AB HIV-infected individuals have an increased prevalence of coronary artery disease. Receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin have been postulated as mediators of vascular calcification. 78 HIV-infected men and 32 healthy controls without history of coronary artery disease were prospectively recruited to undergo cardiac computed tomography and computed tomography angiography to assess coronary artery calcium and plaque burden. Soluble receptor activator of nuclear factor-kappa B ligand was lower in HIV-infected individuals than controls [2.52 (1.08-3.98) vs. 3.33 (2.44-4.64) pg/mL, P = 0.01, median (IQR) respectively]. Soluble receptor activator of nuclear factor-kappa B ligand was negatively associated with the number of coronary segments with plaque (Spearman rho = -0.41, P < 0.001) and Agatston calcium score (rho = -0.30, P < 0.01) in HIV-infected individuals even after adjusting for traditional cardiovascular risk factors. C1 [Hwang, Janice J.; Wei, Jeffrey; Grinspoon, Steven K.; Lo, Janet] Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, Boston, MA 02114 USA. [Hwang, Janice J.; Wei, Jeffrey; Abbara, Suhny; Grinspoon, Steven K.; Lo, Janet] Harvard Univ, Sch Med, Boston, MA USA. [Abbara, Suhny] Massachusetts Gen Hosp, Cardiovasc Imaging Sect, Dept Radiol, Boston, MA 02114 USA. RP Lo, J (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Neuroendocrine Unit, 55 Fruit St,LON207, Boston, MA 02114 USA. EM jlo@partners.org FU NIH [T32 DK007028-37, K23 HL092792, K24 DK064545, F32 HL088991, M01 RR01066-25S1]; Bristol Myers Squibb, Inc. FX Funding was received from NIH T32 DK007028-37 (Dr J.J.H.), K23 HL092792 (Dr J.L.), K24 DK064545 (Dr. S. K. G.), F32 HL088991 (Dr J.L.), M01 RR01066-25S1, and Bristol Myers Squibb, Inc., Funding sources had no role in the design of the study, data analysis or the writing of the article. NR 24 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2012 VL 61 IS 3 BP 359 EP 363 DI 10.1097/QAI.0b013e31826a6c16 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029TR UT WOS:000310519300019 PM 22842843 ER PT J AU Sundararajan, PP AF Sundararajan, Priya Ponnapula TI Transosseous Fixation in Insertional Achilles Tendonitis SO JOURNAL OF FOOT & ANKLE SURGERY LA English DT Article DE Achilles tendon; anchor; bone tunnel; calcaneus; Haglund's deformity ID ROTATOR CUFF REPAIR; ANTERIOR CRUCIATE LIGAMENT; SUTURE ANCHOR FIXATION; TENDON-BONE INTERFACE; IN-VITRO; RETROCALCANEAL BURSITIS; WEAR PARTICLES; RABBIT MODEL; SINGLE-ROW; RECONSTRUCTION AB The surgical approach of severe insertional Achilles tendonitis involves debridement, repair, and reattachment. Previously described techniques for bone-tendon reattachment involved the use of suture anchors in the sparsely trabeculated calcaneus. The following technique tip is a reintroduction of bicortical transosseous fixation previously used in rotator cuff repairs. Bone tunnels are a viable option in the treatment of insertional Achilles tendonitis; however, additional research is necessary to validate its efficacy in this application. (C) 2012 by the American College of Foot and Ankle Surgeons. All rights reserved. C1 [Sundararajan, Priya Ponnapula] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Sundararajan, PP (reprint author), Audie L Murphy Vet Affairs Hosp, 7400 Merton Minter, San Antonio, TX 78229 USA. EM priyaponnapula@gmail.com NR 62 TC 0 Z9 0 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1067-2516 J9 J FOOT ANKLE SURG JI J. Foot Ankle Surg. PD NOV-DEC PY 2012 VL 51 IS 6 BP 806 EP 812 DI 10.1053/j.jfas.2012.06.020 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 027GT UT WOS:000310341000023 PM 22841157 ER PT J AU Parisi, P Striano, P Negro, A Martelletti, P Belcastro, V AF Parisi, Pasquale Striano, Pasquale Negro, Andrea Martelletti, Paolo Belcastro, Vincenzo TI Ictal epileptic headache: an old story with courses and appeals SO JOURNAL OF HEADACHE AND PAIN LA English DT Review DE Cortical spreading depression; Headache; Migraine; Epilepsy; Ictal epileptic headache ID CORTICAL SPREADING DEPRESSION; FAMILIAL HEMIPLEGIC MIGRAINE; IMAGING CHARACTERISTICS; LOBE EPILEPSY; IN-VITRO; MIGRALEPSY; SEIZURES; MECHANISMS; MANIFESTATION; DEFINITION AB The term "ictal epileptic headache" has been recently proposed to classify the clinical picture in which headache is the isolated ictal symptom of a seizure. There is emerging evidence from both basic and clinical neurosciences that cortical spreading depression and an epileptic focus may facilitate each other, although with a different degree of efficiency. This review address the long history which lead to the 'migralepsy' concept to the new emerging pathophysiological aspects, and clinical and electroencephalography evidences of ictal epileptic headache. Here, we review and discuss the common physiopathology mechanisms and the historical aspects underlying the link between headache and epilepsy. Either experimental or clinical measures are required to better understand this latter relationship: the development of animal models, molecular studies defining more precise genotype/phenotype correlations as well as multicenter clinical studies with revision of clinical criteria for headache-/epilepsy-related disorders represent the start of future research. Therefore, the definition of ictal epileptic headache should be used to classify the rare events in which headache is the only manifestation of a seizure. Finally, using our recently published criteria, we will be able to clarify if ictal epileptic headache represents an underestimated phenomenon or not. C1 [Parisi, Pasquale] Univ Roma La Sapienza, NESMOS Dept, Fac Med & Psychol, Headache Paediat Ctr,Chair Paediat,St Andrea Hosp, Rome, Italy. [Striano, Pasquale] Univ Genoa, Pediat Neurol & Muscular Dis Unit, DINOGMI,G Gaslini Inst, Dept Neurosci Rehabil Ophtalmol Genet Maternal &, Genoa, Italy. [Negro, Andrea; Martelletti, Paolo] Univ Roma La Sapienza, Dept Clin & Mol Med, Fac Med & Psychol, Reg Referral Headache Ctr,St Andrea Hosp, Rome, Italy. [Negro, Andrea] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab,Dept Radiol, Boston, MA USA. [Belcastro, Vincenzo] St Anna Hosp, Neurol Clin, Dept Neurosci, Como, Italy. RP Parisi, P (reprint author), Univ Roma La Sapienza, NESMOS Dept, Fac Med & Psychol, Headache Paediat Ctr,Chair Paediat,St Andrea Hosp, Via Grottarossa 1035-1039, Rome, Italy. EM pasquale.parisi@uniroma1.it NR 69 TC 26 Z9 28 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1129-2369 J9 J HEADACHE PAIN JI J. Headache Pain PD NOV PY 2012 VL 13 IS 8 BP 607 EP 613 DI 10.1007/s10194-012-0485-y PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029DI UT WOS:000310474600002 PM 23015297 ER PT J AU Serafini, G Pompili, M Innamorati, M Negro, A Fiorillo, M Lamis, DA Erbuto, D Marsibilio, F Romano, A Amore, M D'Alonzo, L Bozzao, A Girardi, P Martelletti, P AF Serafini, Gianluca Pompili, Maurizio Innamorati, Marco Negro, Andrea Fiorillo, Martina Lamis, Dorian A. Erbuto, Denise Marsibilio, Francesco Romano, Andrea Amore, Mario D'Alonzo, Lidia Bozzao, Alessandro Girardi, Paolo Martelletti, Paolo TI White matter hyperintensities and self-reported depression in a sample of patients with chronic headache SO JOURNAL OF HEADACHE AND PAIN LA English DT Article DE PWMHs; DWMHs; Chronic headache; Self-reported depression; Age ID MAJOR AFFECTIVE-DISORDERS; SCALE CES-D; MOOD DISORDERS; COMMUNITY SAMPLE; PSYCHOMETRIC PROPERTIES; BEHAVIORAL ACTIVATION; GERIATRIC DEPRESSION; TREATMENT RESPONSE; BIS/BAS SCALES; SUICIDE RISK AB White matter hyperintensities (WMH) have been associated with mood disorders in psychiatric patients. In the present study, we aimed to assess whether WMHs are associated with depressive symptoms and different sensitivity of the behavioral inhibition (BIS), and activation (BAS) systems in patients with chronic headache. Participants were 85 adult outpatients (16 men and 69 women) with a diagnosis of chronic headache. All of the patients underwent brain magnetic resonance imaging (MRI) and were administered the BIS/BAS scales and the Center for Epidemiologic Studies Depression Scale. Above 40 % of patients had periventricular WMHs (PWMHs) and almost 98 % had deep WMHs (DWMHs). Patients with PWMHs reported fewer depressive symptoms than patients without PWMHs. Patients with more severe DWMHs (compared with patients with mild or without DWMH lesions) were older and reported lower scores on the drive dimension of the BIS/BAS scales. In multivariate analyses, patients with PWMHs were 1.06 times more likely to report fewer depressive symptoms than patients without PWMHs. WMH lesions in patients with chronic headache were associated with less depression severity. C1 [Serafini, Gianluca; Pompili, Maurizio; Innamorati, Marco; Erbuto, Denise; Girardi, Paolo] Univ Roma La Sapienza, St Andrea Hosp, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, I-00189 Rome, Italy. [Negro, Andrea; Fiorillo, Martina; D'Alonzo, Lidia; Martelletti, Paolo] Univ Roma La Sapienza, Dept Clin & Mol Med, Rome, Italy. [Negro, Andrea; Fiorillo, Martina; Marsibilio, Francesco; D'Alonzo, Lidia; Martelletti, Paolo] St Andrea Hosp, Reg Referral Headache Ctr, Rome, Italy. [Negro, Andrea] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Stroke & Neurovasc Regulat, Boston, MA 02115 USA. [Lamis, Dorian A.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Romano, Andrea; Bozzao, Alessandro] Univ Roma La Sapienza, St Andrea Hosp, Dept Neurosci, Div Neuroradiol, Rome, Italy. [Amore, Mario] Univ Genoa, Sect Psychiat, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy. RP Pompili, M (reprint author), Univ Roma La Sapienza, St Andrea Hosp, Dept Neurosci Mental Hlth & Sensory Organs, Suicide Prevent Ctr, 1035-1039 Via Grottarossa, I-00189 Rome, Italy. EM maurizio.pompili@uniroma1.it RI Innamorati, Marco/H-8877-2013; OI Innamorati, Marco/0000-0003-1389-2290; Pompili, Maurizio/0000-0003-1886-4977; Erbuto, Denise/0000-0002-6403-7254 NR 63 TC 7 Z9 7 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1129-2369 J9 J HEADACHE PAIN JI J. Headache Pain PD NOV PY 2012 VL 13 IS 8 BP 661 EP 667 DI 10.1007/s10194-012-0493-y PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 029DI UT WOS:000310474600008 PM 23080079 ER PT J AU Farley, K Stolley, JM Zhao, PC Cooley, J Remold-O'Donnell, E AF Farley, Kalamo Stolley, J. Michael Zhao, Picheng Cooley, Jessica Remold-O'Donnell, Eileen TI A SerpinB1 Regulatory Mechanism Is Essential for Restricting Neutrophil Extracellular Trap Generation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INNATE IMMUNITY; HISTONE DEIMINATION; SERINE PROTEASES; BONE-MARROW; INHIBITOR; GRANULOCYTES; ELASTASE; DIPHENYLENEIODONIUM; ACTIVATION; LEUKOCYTES AB NETosis (neutrophil extracellular trap [NET] generation), a programmed death pathway initiated in mature neutrophils by pathogens and inflammatory mediators, can be a protective process that sequesters microbes and prevents spread of infection, but it can also be a pathological process that causes inflammation and serious tissue injury. Little is known about the regulatory mechanism. Previously, we demonstrated that serpinb1-deficient mice are highly susceptible to pulmonary bacterial and viral infections due to inflammation and tissue injury associated with increased neutrophilic death. In this study, we used in vitro and in vivo approaches to investigate whether SerpinB1 regulates NETosis. We found that serpinb1-deficient bone marrow and lung neutrophils are hypersusceptible to NETosis induced by multiple mediators in both an NADPH-dependent and -independent manner, indicating a deeply rooted regulatory role in NETosis. This role is further supported by increased nuclear expansion (representing chromatin decondensation) of PMA-treated serpinb1-deficient neutrophils compared with wild-type, by migration of SerpinB1 from the cytoplasm to the nucleus of human neutrophils that is coincident with or preceding early conversion of lobulated (segmented) nuclei to delobulated (spherical) morphology, as well as by the finding that exogenous human recombinant SerpinB1 abrogates NET production. NETosis of serpinb1-deficient neutrophils is also increased in vivo during Pseudomonas aeruginosa lung infection. The findings identify a previously unrecognized regulatory mechanism involving SerpinB1 that restricts the production of NETs. The Journal of Immunology, 2012, 189: 4574-4581. C1 [Farley, Kalamo; Stolley, J. Michael; Zhao, Picheng; Cooley, Jessica; Remold-O'Donnell, Eileen] Boston Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Farley, Kalamo; Zhao, Picheng; Remold-O'Donnell, Eileen] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Remold-O'Donnell, Eileen] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Remold-O'Donnell, E (reprint author), Boston Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, 3 Blackfan Circle, Boston, MA 02115 USA. EM remold@idi.harvard.edu RI ZHAO, PICHENG/G-3737-2014 FU National Heart, Lung and Blood Institute Grant [HL-066548]; National Institute of Allergy and Infectious Diseases Grant [AI-072552] FX This work was supported by National Heart, Lung and Blood Institute Grant HL-066548 and National Institute of Allergy and Infectious Diseases Grant AI-072552. NR 40 TC 25 Z9 27 U1 0 U2 14 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2012 VL 189 IS 9 BP 4574 EP 4581 DI 10.4049/jimmunol.1201167 PG 8 WC Immunology SC Immunology GA 025OO UT WOS:000310200600045 PM 23002442 ER PT J AU Elvington, A Atkinson, C Zhu, H Yu, J Takahashi, K Stahl, GL Kindy, MS Tomlinson, S AF Elvington, Andrew Atkinson, Carl Zhu, Hong Yu, Jin Takahashi, Kazue Stahl, Gregory L. Kindy, Mark S. Tomlinson, Stephen TI The Alternative Complement Pathway Propagates Inflammation and Injury in Murine Ischemic Stroke SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MANNOSE-BINDING LECTIN; FOCAL CEREBRAL-ISCHEMIA; NEURONAL CELL-DEATH; REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; BRAIN-INJURY; TARGETED DELETION; ARTERY OCCLUSION; MICE; ACTIVATION AB There is mounting evidence indicating an important role for complement in the pathogenesis of cerebral ischemia-reperfusion injury, or ischemic stroke. The role of the alternative complement pathway in ischemic stroke has not been investigated, and there is conflicting data on the role of the terminal pathway. In this study, we show that compared with wild-type mice, mice deficient in the alternative pathway protein factor B or mice treated with the alternative pathway inhibitor CR2-fH have improved outcomes after 60-min middle cerebral artery occlusion and 24-h reperfusion. Factor B-deficient or CR2-fH-treated mice were protected in terms of improved neurologic function and reduced cerebral infarct, demyelination, P-selectin expression, neutrophil infiltration, and microthrombi formation. Mice deficient in both the classical and lectin pathways (C1q/MBL deficient) were also protected from cerebral ischemia-reperfusion injury, and there was no detectable C3d deposition in the ipsilateral brain of these mice. These data demonstrate that the alternative pathway is not alone sufficient to initiate complement activation and indicate that the alternative pathway propagates cerebral injury via amplification of the cascade. Deficiency of C6, a component of the terminal cytolytic membrane attack complex, had no effect on outcome after ischemic stroke, indicating that the membrane attack complex is not involved in mediating injury in this model. We additionally show that the protective effect of factor B deficiency and CR2-fH treatment is sustained in the subacute stage of infarct development, adding to the clinical relevance of these findings. The Journal of Immunology, 2012, 189: 4640-4647. C1 [Elvington, Andrew; Atkinson, Carl; Tomlinson, Stephen] Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Zhu, Hong; Yu, Jin; Kindy, Mark S.] Med Univ S Carolina, Inst Neurosci, Dept Neurosci, Charleston, SC 29425 USA. [Takahashi, Kazue] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Stahl, Gregory L.] Harvard Univ, Sch Med, Harvard Inst Med, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA 02115 USA. [Kindy, Mark S.; Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Childrens Res Inst, Dept Microbiol & Immunol, 173 Ashley Ave,BSB 201, Charleston, SC 29401 USA. EM tomlinss@musc.edu FU National Institutes of Health [HL082485, HL86576]; Department of Veterans Affairs (Merit Award) [NURC-051010F]; Alexion Pharmaceuticals, a company developing complement inhibitory therapeutics FX This work was supported by grants from the National Institutes of Health (HL082485, HL86576) and the Department of Veterans Affairs (Merit Award NURC-051010F).; S.T. has received research support from Alexion Pharmaceuticals, a company developing complement inhibitory therapeutics. The other authors have no financial conflicts of interest. NR 53 TC 28 Z9 30 U1 0 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2012 VL 189 IS 9 BP 4640 EP 4647 DI 10.4049/jimmunol.1201904 PG 8 WC Immunology SC Immunology GA 025OO UT WOS:000310200600052 PM 23028050 ER PT J AU Reeves, RK Evans, TI Gillis, J Wong, FE Kang, GB Li, QS Johnson, RP AF Reeves, R. Keith Evans, Tristan I. Gillis, Jacqueline Wong, Fay E. Kang, Guobin Li, Qingsheng Johnson, R. Paul TI SIV Infection Induces Accumulation of Plasmacytoid Dendritic Cells in the Gut Mucosa SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY VIRUS-INFECTION; ALPHA-INTERFERON PRODUCTION; NK CELLS; T-CELLS; ACTIVATION AB Multiple studies suggest that plasmacytoid dendritic cells (pDCs) are depleted and dysfunctional during human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but little is known about pDCs in the gut-the primary site of virus replication. Here, we show that during SIV infection, pDCs were reduced 3-fold in the circulation and significantly upregulated the gut-homing marker alpha 4 beta 7, but were increased 4-fold in rectal biopsies of infected compared to naive macaques. These data revise the understanding of pDC immunobiology during SIV infection, indicating that pDCs are not necessarily depleted, but instead may traffic to and accumulate in the gut mucosa. C1 [Reeves, R. Keith; Evans, Tristan I.; Gillis, Jacqueline; Wong, Fay E.; Johnson, R. Paul] Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, Southborough, MA 01772 USA. [Kang, Guobin; Li, Qingsheng] Univ Nebraska Lincoln Nebraska, Nebraska Ctr Virol, Lincoln, NE USA. [Kang, Guobin; Li, Qingsheng] Univ Nebraska Lincoln Nebraska, Sch Biol Sci, Lincoln, NE USA. [Johnson, R. Paul] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Johnson, R. Paul] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Boston, MA USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, Div Immunol, New England Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM paul_johnson@hms.harvard.edu FU National Institutes of Health [AI071306, AI090735, RR00168]; Center for HIV/AIDS Vaccine Immunology/HIV Vaccine Trials Network Early Career Investigator award [U19 AI 067854-07] FX This work was supported by the National Institutes of Health grants AI071306, AI090735, RR00168, and a Center for HIV/AIDS Vaccine Immunology/HIV Vaccine Trials Network Early Career Investigator award (U19 AI 067854-07 to R. K. R.). NR 18 TC 43 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2012 VL 206 IS 9 BP 1462 EP 1468 DI 10.1093/infdis/jis408 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 022BT UT WOS:000309930700019 PM 22711907 ER PT J AU Ge, Y Wang, TJ AF Ge, Y. Wang, T. J. TI Identifying novel biomarkers for cardiovascular disease risk prediction SO JOURNAL OF INTERNAL MEDICINE LA English DT Review DE biomarker; cardiovascular disease risk factors; prevention ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; INTIMA-MEDIA THICKNESS; LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE-A2; MINOR ECG ABNORMALITIES; ANKLE-BRACHIAL INDEX; SERVICES TASK-FORCE; ARTERY-DISEASE; ATHEROSCLEROSIS RISK; MORTALITY RISK AB The primary prevention of cardiovascular disease relies on the ability to identify at-risk individuals long before the development of overt events. In the past decade, research into circulating, genetic and imaging biomarkers to augment traditional methods of risk prediction has only achieved modest success. Emerging technologies in the fields of genomics, metabolomics and proteomics are providing new platforms for biomarker discovery. Here, we review current concepts in the evaluation and discovery of cardiovascular biomarkers. Further research is needed to identify new biomarkers to successfully stratify risk of cardiovascular disease in low-risk populations, as well as to test whether management strategies informed by biomarker testing are better than standard of care. C1 [Ge, Y.; Wang, T. J.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA 02114 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org FU Siemens; Brahms; Critical Diagnostics; Singulex; Diasorin; Pfizer; Roche; LabCorp FX Dr Wang has been part of the scientific advisory board of Diasorin Inc., has received technical support or research funding from Siemens, Brahms, Critical Diagnostics, Singulex, Diasorin, Pfizer, Roche and LabCorp and has received honoraria from Roche, Diasorin and Quest Diagnostics. Dr Wang is named as a co-inventor on patent applications relating to the use of metabolomic or neurohormonal biomarkers in risk prediction. NR 81 TC 16 Z9 17 U1 1 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD NOV PY 2012 VL 272 IS 5 BP 430 EP 439 DI 10.1111/j.1365-2796.2012.02589.x PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 027XT UT WOS:000310388100002 PM 22950687 ER PT J AU Delpolyi, AR Wu, O Macklin, EA Schaefer, PW Schwamm, LH Gonzalez, RG Copen, WA AF Delpolyi, Amy R. Wu, Ona Macklin, Eric A. Schaefer, Pamela W. Schwamm, Lee H. Gonzalez, R. Gilberto Copen, William A. TI Reliability of cerebral blood volume maps as a substitute for diffusion-weighted imaging in acute ischemic stroke SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE stroke; perfusion weighted imaging; cerebral blood volume; diffusion weighted imaging ID HYPERACUTE STROKE; MRI; CONTRAST; DISEASE; CT; DESMOTEPLASE; THROMBOLYSIS; REPERFUSION; PREDICTION; INFARCTION AB Purpose: To assess the reliability of cerebral blood volume (CBV) maps as a substitute for diffusion-weighted MRI (DWI) in acute ischemic stroke. In acute stroke, DWI is often used to identify irreversibly injured core tissue. Some propose using perfusion imaging, specifically CBV maps, in place of DWI. We examined whether CBV maps can reliably subsitute for DWI, and assessed the effect of scan duration on calculated CBV. Materials and Methods: We retrospectively identified 58 patients who underwent DWI and MR perfusion imaging within 12 h of stroke onset. CBV in each DWI lesion's center was divided by CBV in the normal-appearing contralateral hemisphere to yield relative regional CBV (rrCBV). The proportion of lesions with decreased rrCBV was calculated. After using the full scan duration (110 s after contrast injection), rrCBV was recalculated using simulated shorter scans. The effect of scan duration on rrCBV was tested with linear regression. Results: Using the full scan duration (110 s), rrCBV was increased in most DWI lesions (62%; 95% confidence interval, 4874%). rrCBV increased with increasing scan duration (P < 0.001). Even with the shortest duration (39.5 s) rrCBV was increased in 33% of lesions. Conclusion: Because DWI lesions may have elevated or decreased CBV, CBV maps cannot reliably substitute for DWI in identifying the infarct core. J. Magn. Reson. Imaging 2012;36:10831087. (c) 2012 Wiley Periodicals, Inc. C1 [Delpolyi, Amy R.; Wu, Ona; Schaefer, Pamela W.; Gonzalez, R. Gilberto; Copen, William A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Delpolyi, Amy R.; Wu, Ona; Macklin, Eric A.; Schaefer, Pamela W.; Schwamm, Lee H.; Gonzalez, R. Gilberto; Copen, William A.] Harvard Univ, Sch Med, Boston, MA USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Copen, WA (reprint author), Massachusetts Gen Hosp, Dept Radiol, GRB 273A,55 Fruit St, Boston, MA 02114 USA. EM wcopen@partners.org RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Schwamm, Lee/0000-0003-0592-9145; Deipolyi, Amy/0000-0003-3144-386X FU NIH [R01NS059775, R01NS050041, UL1RR02758]; Harvard Catalyst/Harvard Clinical and Translational Science Center by means of the NIH; Harvard University FX Contract grant sponsor: NIH; Contract grant numbers: R01NS059775, R01NS050041, UL1RR02758.; This work was supported by and Harvard Catalyst/Harvard Clinical and Translational Science Center by means of the NIH and financial contributions from Harvard University and its affiliated academic health care centers. Content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Center for Research Resources, or the National Institutes of Health. NR 27 TC 10 Z9 11 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2012 VL 36 IS 5 BP 1083 EP 1087 DI 10.1002/jmri.23740 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 027ZO UT WOS:000310392800007 PM 22761110 ER PT J AU Adair, JE Zhao, X Chien, S Fang, M Wohlfahrt, ME Trobridge, GD Taylor, JA Beard, BC Kiem, HP Becker, PS AF Adair, Jennifer E. Zhao, Xin Chien, Sylvia Fang, Min Wohlfahrt, Martin E. Trobridge, Grant D. Taylor, Jason A. Beard, Brian C. Kiem, Hans-Peter Becker, Pamela S. TI Cyclophosphamide promotes engraftment of gene-modified cells in a mouse model of Fanconi anemia without causing cytogenetic abnormalities SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE Gene therapy; Fanconi anemia; Lentivirus vector; Cyclophosphamide; Autologous transplantation ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; HEMATOPOIETIC PROGENITOR CELLS; LOW-DOSE CYCLOPHOSPHAMIDE; DNA CROSS-LINKING; IN-VIVO; GROUP-A; GROUP-C; CONDITIONING REGIMEN; REPOPULATING CELLS AB A major hurdle for hematopoietic stem cell (HSC) gene therapy for inherited bone marrow disorders, including Fanconi anemia (FA), is adequate engraftment of gene-modified cells. A phenotypic defect in DNA repair renders FA patients sensitive to alkylating agents such as cyclophosphamide (Cy); however, at lower doses, Cy is well tolerated in the FA transplant setting. We tested whether non-alkylating agents could replace Cy for pretransplant conditioning to enhance engraftment of FANCA gene-modified hematopoietic cells. We compared Cy preconditioning with fludarabine (Flu) or cytarabine (AraC) or no conditioning as a control in fanca (-/-) mutant mice receiving gene-modified bone marrow cells. Only mice conditioned with Cy exhibited appreciable engraftment of gene-modified cells by PCR and resistance to mitomycin C (MMC). Cy administration following transplantation increased gene marking levels in all animals treated, but highest gene marking and corresponding MMC resistance were observed in mice receiving Cy pre- and posttransplantation. Importantly, no cytogenetic abnormalities were observed in Cy-treated mice. We conclude that Cy is an effective and superior preparative regimen with respect to engraftment of lentivirus-transduced cells and functional correction in fanca (-/-) mice. Thus, appropriately dosed Cy may provide a suitable conditioning regimen for FA patients undergoing HSC gene therapy. C1 [Adair, Jennifer E.; Wohlfahrt, Martin E.; Beard, Brian C.; Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Zhao, Xin; Chien, Sylvia] Univ Washington, Div Hematol, Dept Med, Seattle, WA 98109 USA. [Fang, Min] Seattle Canc Care Alliance, Dept Med, Div Pathol, Seattle, WA 98109 USA. [Trobridge, Grant D.] Washington State Univ, Dept Pharmaceut Sci, Pullman, WA 99164 USA. [Taylor, Jason A.] Portland VA Med Ctr, Portland, OR 97239 USA. [Beard, Brian C.] Univ Washington, Div Med Oncol, Dept Med, Seattle, WA 98195 USA. [Kiem, Hans-Peter] Univ Washington, Sch Med, Div Hematol, Seattle, WA 98195 USA. [Kiem, Hans-Peter] Univ Washington, Sch Med, Div Pathol, Seattle, WA 98195 USA. [Becker, Pamela S.] Univ Washington, Inst Stem Cell & Regenerat Med, Seattle, WA 98109 USA. RP Kiem, HP (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N, Seattle, WA 98109 USA. EM hkiem@fhcrc.org; pbecker@u.washington.edu FU National Institutes of Health, Bethesda, MD, USA [P30 DK056465, P01 HL036444, R01 HL085693] FX The authors are grateful for research funding from the National Institutes of Health, Bethesda, MD, USA, grants P30 DK056465, P01 HL036444, and R01 HL085693. H.-P. Kiem is a Markey Molecular Medicine Investigator and the recipient of the Jose Carreras/E. Donnall Thomas Endowed Chair for Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health nor its subsidiary Institutes and Centers NR 35 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED JI J. Mol. Med. PD NOV PY 2012 VL 90 IS 11 BP 1283 EP 1294 DI 10.1007/s00109-012-0905-0 PG 12 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 025XT UT WOS:000310231300006 PM 22660274 ER PT J AU Gobel, A Macklin, EA Winkler, S Betensky, RA Klein, C Lohmann, K Simon, DK AF Goebel, Anna Macklin, Eric A. Winkler, Susen Betensky, Rebecca A. Klein, Christine Lohmann, Katja Simon, David K. TI Genetic risk factors in Parkinson's disease: single gene effects and interactions of genotypes SO JOURNAL OF NEUROLOGY LA English DT Letter ID PATHOGENESIS; ASSOCIATION; ROLES C1 [Goebel, Anna; Winkler, Susen; Klein, Christine; Lohmann, Katja] Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, D-23538 Lubeck, Germany. [Macklin, Eric A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Simon, David K.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Beaconess Ctr, Boston, MA 02115 USA. RP Lohmann, K (reprint author), Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM katja.lohmann@neuro.uni-luebeck.de RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU NCI NIH HHS [R01 CA075971]; NIA NIH HHS [P50 AG005134]; NINDS NIH HHS [T32 NS048005] NR 13 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD NOV PY 2012 VL 259 IS 11 BP 2503 EP 2505 DI 10.1007/s00415-012-6623-2 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 029CJ UT WOS:000310472100038 PM 22878430 ER PT J AU Gregory, JL Prada, CM Fine, SJ Garcia-Alloza, M Betensky, RA Arbel-Ornath, M Greenberg, SM Bacskai, BJ Frosch, MP AF Gregory, Julia L. Prada, Claudia M. Fine, Sara J. Garcia-Alloza, Monica Betensky, Rebecca A. Arbel-Ornath, Michal Greenberg, Steven M. Bacskai, Brian J. Frosch, Matthew P. TI Reducing Available Soluble beta-Amyloid Prevents Progression of Cerebral Amyloid Angiopathy in Transgenic Mice SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer; Amyloid; Cerebral amyloid angiopathy; Cerebrovasculature; Gamma secretase; Gelsolin; Imaging; Multiphoton ID GAMMA-SECRETASE INHIBITOR; PLASMA A-BETA; ALZHEIMER-DISEASE; MOUSE MODEL; CEREBROSPINAL-FLUID; IN-VIVO; MULTIPHOTON MICROSCOPY; BRAIN; IMMUNOTHERAPY; GELSOLIN AB Cerebral amyloid angiopathy (CAA), the accumulation of beta-amyloid (A beta) in the walls of leptomeningeal and cortical blood vessels of the brain, is a major cause of intracerebral hemorrhage and cognitive impairment and is commonly associated with Alzheimer disease. The progression of CAA, as measured in transgenic mice by longitudinal imaging with multiphoton microscopy, occurs in a predictable linear manner. The dynamics of A beta deposition in and clearance from vascular walls and their relationship to the concentration of A beta in the brain are poorly understood. We manipulated A beta levels in the brain using 2 approaches: peripheral clearance via administration of the amyloid binding "peripheral sink'' protein gelsolin and direct inhibition of its formation via administration of LY-411575, a small-molecule gamma-secretase inhibitor. We found that gelsolin and LY-411575 both reduced the rate of CAA progression in Tg2576 mice from untreated rates of 0.58% +/- 0.15% and 0.52% +/- 0.09% to 0.11% +/- 0.18% (p = 0.04) and -0.17% +/- 0.09% (p < 0.001) of affected vessel per day, respectively, in the absence of an immune response. The progression of CAA was also halted when gelsolin was combined with LY-411575 (-0.004% +/- 0.10%, p < 0.003). These data suggest that CAA progression can be prevented with non-immune approaches that may reduce the availability of soluble A beta but without evidence of substantial amyloid clearance from vessels. C1 [Gregory, Julia L.; Prada, Claudia M.; Fine, Sara J.; Garcia-Alloza, Monica; Arbel-Ornath, Michal; Greenberg, Steven M.; Bacskai, Brian J.; Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, Charlestown, MA 02129 USA. [Garcia-Alloza, Monica] Univ Cadiz, Sch Med, Div Physiol, Cadiz, Spain. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM bbacskai@partners.org RI Gregory, Julia/K-8726-2012 FU National Institutes of Health [EB00768, AG021084, AG005134]; Harvard NeuroDiscovery Center; ISCIII Subdireccion General de Evaluacion y Fomento de la Investigacion [PS09/00969]; Proyectos Excelencia Junta Adalucia [CTS-7847]; Fundacion Dr. Eugenio Rodriguez Pascual; [Ramon y Cajal-2008-02333] FX This work was supported by the National Institutes of Health (EB00768 to Brian Bacskai; AG021084 and AG005134 to Matthew Frosch); Harvard NeuroDiscovery Center (to Rebecca Betensky); and Ramon y Cajal-2008-02333, PN I + D + I 2008-2011; ISCIII Subdireccion General de Evaluacion y Fomento de la Investigacion PS09/00969, Proyectos Excelencia Junta Adalucia 2011: CTS-7847, Fundacion Dr. Eugenio Rodriguez Pascual (to Monica Garcia-Alloza). NR 44 TC 7 Z9 8 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2012 VL 71 IS 11 BP 1009 EP 1017 DI 10.1097/NEN.0b013e3182729845 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 030CF UT WOS:000310544800007 PM 23095848 ER PT J AU Delgado-Borrego, A Smith, L Jonas, MM Hall, CA Negre, B Jordan, SH Ogrodowicz, M Raza, R Ludwig, DA Miller, T Lipshultz, SE Gonzalez-Peralta, R Chung, RT AF Delgado-Borrego, Aymin Smith, Lesley Jonas, Maureen M. Hall, Cyndena A. Negre, Betania Jordan, Sergio H. Ogrodowicz, Matthew Raza, Roshan Ludwig, David A. Miller, Tracie Lipshultz, Steven E. Gonzalez-Peralta, Regino Chung, Raymond T. TI Expected and Actual Case Ascertainment and Treatment Rates for Children Infected with Hepatitis C in Florida and the United States: Epidemiologic Evidence from Statewide and Nationwide Surveys SO JOURNAL OF PEDIATRICS LA English DT Article ID VIRUS-INFECTION; EXTRAHEPATIC MANIFESTATIONS; HEPATOCELLULAR-CARCINOMA; LIVER-DISEASE; DRUG-USERS; PREVALENCE; MANAGEMENT; PATHOLOGY; BARRIERS; BURDEN AB Objective To evaluate the rate of pediatric hepatitis C virus (HCV) case ascertainment relative to the estimated number of actual cases. Study design Data from Florida and United States health departments were used to assess pediatric HCV case ascertainment rates in Florida and nationwide. The percentage of children infected with HCV from Miami-Dade County receiving medical care by a pediatric gastroenterologist was estimated based on data obtained from physician questionnaires. Results From 2000 through 2009, 2007 children were identified as having positive HCV antibody tests in Florida, only 12% of the expected number (n = 12 155). An estimated 1.6% of the expected children with HCV who tested Ab-positive (37 of 1935) were actively followed by a pediatric gastroenterologist in Miami-Dade County, Florida. Across the United States, only 4.9% of the expected cases have been identified. Conclusions The identification of children infected with HCV in the nation as a whole is grossly inadequate. Only a small fraction of cases are identified. In Florida, less than 2% of children identified receive treatment. Lack of identification and lack of treatment of children infected with HCV constitute critical public health problems. Strategies to increase awareness of HCV infection and to screen at-risk individuals could substantially improve morbidity and mortality while reducing health care costs. (J Pediatr 2012;161:915-21). C1 [Delgado-Borrego, Aymin; Negre, Betania; Jordan, Sergio H.; Ludwig, David A.; Miller, Tracie; Lipshultz, Steven E.] Univ Miami, Miller Sch Med, Batchelor Childrens Res Inst, Dept Pediat, Miami, FL 33136 USA. [Delgado-Borrego, Aymin; Smith, Lesley; Miller, Tracie] Univ Miami, Miller Sch Med, Dept Pediat, Div Gastroenterol & Hepatol, Miami, FL 33136 USA. [Delgado-Borrego, Aymin; Jonas, Maureen M.; Ogrodowicz, Matthew; Raza, Roshan] Childrens Hosp, Div Pediat Gastroenterol Hepatol & Nutr, Boston, MA 02115 USA. [Gonzalez-Peralta, Regino] Univ Florida, Coll Med, Gainesville, FL USA. [Gonzalez-Peralta, Regino] Shands Childrens Hosp, Dept Pediat, Gainesville, FL USA. [Hall, Cyndena A.] Dept Hlth, Tallahassee, FL USA. [Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp, Boston, MA USA. RP Delgado-Borrego, A (reprint author), Univ Miami, Miller Sch Med, Batchelor Childrens Res Inst, Dept Pediat, 1580 NW 10th Ave,Room 523, Miami, FL 33136 USA. EM adelgado5@med.miami.edu NR 32 TC 8 Z9 8 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2012 VL 161 IS 5 BP 915 EP 921 DI 10.1016/j.jpeds.2012.05.002 PG 7 WC Pediatrics SC Pediatrics GA 027RJ UT WOS:000310370600031 PM 22765955 ER PT J AU Arakaki, R Shofner, JD Kroshinsky, D AF Arakaki, Ryan Shofner, Joshua D. Kroshinsky, Daniela TI An Infant with Pulmonary-Cutaneous Sweet Syndrome SO JOURNAL OF PEDIATRICS LA English DT Article ID FEBRILE NEUTROPHILIC DERMATOSIS; DISEASE; CHILD AB We report the case of a 31-day-old girl presenting with severe respiratory distress and cutaneous lesions from Sweet syndrome. Pulmonary symptoms unresponsive to antibiotics in patients with Sweet syndrome should raise suspicion for neutrophilic infiltration. (J Pediatr 2012;161:959-61). C1 [Arakaki, Ryan] Harvard Univ, Sch Med, Boston, MA USA. [Shofner, Joshua D.; Kroshinsky, Daniela] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Arakaki, R (reprint author), 28 St Albans Rd,2, Boston, MA 02115 USA. EM ryan_arakaki@hms.harvard.edu NR 19 TC 1 Z9 2 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2012 VL 161 IS 5 BP 959 EP 961 DI 10.1016/j.jpeds.2012.07.035 PG 3 WC Pediatrics SC Pediatrics GA 027RJ UT WOS:000310370600039 PM 22929161 ER PT J AU Rahimpour, S Nezami, BG Karimian, N Sotoudeh-Anvari, M Ebrahimi, F Taleb, S Mirazi, N Dehpour, AR AF Rahimpour, Sina Nezami, Behtash Ghazi Karimian, Negin Sotoudeh-Anvari, Maryam Ebrahimi, Farzad Taleb, Shayandokht Mirazi, Naser Dehpour, Ahmad Reza TI Hypothyroidism improves random-pattern skin flap survival in rats SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Hypothyroidism; Surgical flaps; Propylthiouracil; Methimazole; Ischemia/prevention & control ID METHIMAZOLE-INDUCED HYPOTHYROIDISM; NITRIC-OXIDE; ISCHEMIA-REPERFUSION; EXPERIMENTAL COLITIS; TOPICAL METHIMAZOLE; THYROID-DISEASE; LIVER-DAMAGE; PROPYLTHIOURACIL; INJURY; MODEL AB Background: The protective effect of hypothyroidism against ischemic or toxic conditions has been shown in various tissues. We investigated the effect of propylthiouracil (PTU)/methimazole (MMI)-induced hypothyroidism and acute local effect of MMI on the outcome of lethal ischemia in random-pattern skin flaps. Materials and methods: Dorsal flaps with caudal pedicles were elevated at midline and flap survival was measured at the seventh day after surgery. The first group, as control, received 1 mL of 0.9% saline solution in the flap before flap elevation. In groups 2 and 3, hypothyroidism was induced by administration of either PTU 0.05% or MMI 0.04% in drinking water. The next four groups received local injections of MMI (10, 20, 50, or 100 mu g/flap) before flap elevation. Local PTU injection was ignored due to insolubility of the agent. Results: Hypothyroidism was induced in chronic PTU- and MMI-treated groups, and animals in these groups showed significant increase in their flap survival, compared to control euthyroid rats (79.47% +/- 10.49% and 75.48% +/- 12.93% versus 52.26% +/- 5.75%, respectively, P < 0.01). Acute local treatment of skin flaps with MMI failed to significantly affect the flap survival. Conclusion: This study demonstrates for the first time that hypothyroidism improves survival of random-pattern skin flaps in rats. (C) 2012 Elsevier Inc. All rights reserved. C1 [Rahimpour, Sina; Nezami, Behtash Ghazi; Karimian, Negin; Taleb, Shayandokht; Dehpour, Ahmad Reza] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran. [Nezami, Behtash Ghazi] Emory Univ, Sch Med, Div Digest Dis, Atlanta, GA USA. [Nezami, Behtash Ghazi] VAMC, Atlanta, GA USA. [Sotoudeh-Anvari, Maryam] Univ Tehran Med Sci, Tehran Heart Ctr, Dept Surg & Clin Pathol, Tehran, Iran. [Ebrahimi, Farzad] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Mirazi, Naser] Bou Ali Sina Univ, Dept Biol, Hamehan, Iran. RP Dehpour, AR (reprint author), Univ Tehran Med Sci, Sch Med, Dept Pharmacol, POB 13145-784, Tehran, Iran. EM dehpour@yahoo.com OI dehpour, ahmad reza/0000-0002-8001-5565 NR 39 TC 0 Z9 0 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 2012 VL 178 IS 1 BP 524 EP 528 DI 10.1016/j.jss.2012.03.058 PG 5 WC Surgery SC Surgery GA 028UV UT WOS:000310450300077 PM 22521221 ER PT J AU Stone, RA Sevick, MA Rao, RH Macpherson, DS Cheng, CR Kim, S Hough, LJ DeRubertis, FR AF Stone, Roslyn A. Sevick, Mary Ann Rao, R. Harsha Macpherson, David S. Cheng, Chunrong Kim, Sunghee Hough, Linda J. DeRubertis, Frederick R. TI The Diabetes Telemonitoring Study Extension: an exploratory randomized comparison of alternative interventions to maintain glycemic control after withdrawal of diabetes home telemonitoring SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID CONTROLLED-TRIAL; BLOOD-GLUCOSE; TELEMEDICINE SUPPORT; COLLABORATIVE CARE; FOLLOW-UP; MANAGEMENT; TIME; TRANSMISSION; REDUCTION; TELECARE AB Background Telemonitoring interventions featuring transmission of home glucose records to healthcare providers have resulted in improved glycemic control in patients with diabetes. No research has addressed the intensity or duration of telemonitoring required to sustain such improvements. Purpose The DiaTel study (10 January 2005 to 1 November 2007) compared active care management (ACM) with home telemonitoring (n=73) to monthly care coordination (CC) telephone calls (n=77) among veterans with diabetes and suboptimal glycemic control. The purpose of the Dia Tel Extension was to assess whether initial improvements could be sustained with interventions of the same or lower intensity among participants who re-enrolled in a 6-month extension of DiaTel. Methods Dia Tel participants receiving ACM were re-assigned randomly to monthly CC calls with continued telemonitoring but no active medication management (ACM-to-CCHT, n=23) or monthly CC telephone calls (ACM-to-CC, n=21). Dia Tel participants receiving CC were re-assigned randomly to continued CC (CC-to-CC, n=28) or usual care (UC, ie, CC-to-UC, n=29). Hemaglobin A1c (HbA1c) was assessed at 3 and 6 months following re-randomization. Results Marked HbA1c improvements observed in DiaTel ACM participants were sustained 6 months after re-randomization in both ACM-to-CCHT and ACM-to-CC groups. Lesser HbA1c improvements observed in DiaTel CC participants were sustained in both CC-to-CC and CC-to-UC groups. No benefit was apparent for continued transmission of glucose data among DiaTel ACM participants or continued monthly telephone calls among DiaTel CC participants 6 months after re-randomization. Conclusion Significant improvements in HbA1c achieved using home telemonitoring and active medication management for 6 months were sustained 6 months later with interventions of decreased intensity in VA Health System-qualified veterans. C1 [Rao, R. Harsha; DeRubertis, Frederick R.] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA. [Stone, Roslyn A.; Sevick, Mary Ann; Cheng, Chunrong; Kim, Sunghee] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Stone, Roslyn A.; Cheng, Chunrong; Kim, Sunghee] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Sevick, Mary Ann; Rao, R. Harsha; Macpherson, David S.; DeRubertis, Frederick R.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Sevick, Mary Ann] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Sevick, Mary Ann] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Macpherson, David S.] VISN 4 Healthcare Network, Pittsburgh, PA USA. [Hough, Linda J.] Vet Res Fdn Pittsburgh, Pittsburgh, PA USA. RP DeRubertis, FR (reprint author), VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Univ Dr C 111-U, Pittsburgh, PA 15240 USA. EM frederick.derubertis@va.gov FU US Air Force [W81XWH-04-2-0030]; Viterion TeleHealthcare, LLC; Tarrytown, New York FX This work was supported by award W81XWH-04-2-0030 from the US Air Force, administered by the US Army Medical Research Acquisition Activity, Fort Detrick, Maryland, and by resources and the use of facilities at the VA Pittsburgh Healthcare System. A portion of the telemonitoring and other equipment costs were supported by Viterion TeleHealthcare, LLC; Tarrytown, New York. The funding agencies played no role in the conduct or reporting of this study. NR 34 TC 11 Z9 12 U1 0 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2012 VL 19 IS 6 BP 973 EP 979 DI 10.1136/amiajnl-2012-000815 PG 7 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 028FP UT WOS:000310408500009 PM 22610495 ER PT J AU Russ, AL Weiner, M Saleem, JJ Wears, RL AF Russ, Alissa L. Weiner, Michael Saleem, Jason J. Wears, Robert L. TI When 'technically preventable' alerts occur, the design-not the prescriber-has failed SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Letter C1 [Russ, Alissa L.; Weiner, Michael; Saleem, Jason J.] US Dept Vet Affairs, Ctr Excellence Implementing Evidence Based Practi, Richard L Roudebush VA Med Ctr, Vet Hlth Adm,Hlth Serv Res & Dev Serv HFP 04 148, Indianapolis, IN 46254 USA. [Russ, Alissa L.; Weiner, Michael; Saleem, Jason J.] Regenstrief Inst Inc, Indianapolis, IN USA. [Russ, Alissa L.; Weiner, Michael; Saleem, Jason J.] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA. [Russ, Alissa L.] Purdue Univ, Sch Pharm, Dept Pharm Practice, W Lafayette, IN 47907 USA. [Wears, Robert L.] Univ Florida, Dept Emergency Med, Jacksonville, FL USA. [Wears, Robert L.] Univ London Imperial Coll Sci Technol & Med, Clin Safety Res Unit, London, England. RP Russ, AL (reprint author), US Dept Vet Affairs, Ctr Excellence Implementing Evidence Based Practi, Richard L Roudebush VA Med Ctr, Vet Hlth Adm,Hlth Serv Res & Dev Serv HFP 04 148, Indianapolis, IN 46254 USA. EM alissa.russ@va.gov OI Wears, Robert/0000-0001-9826-954X FU AHRQ HHS [R18 HS017902]; NCATS NIH HHS [UL1 TR000064] NR 5 TC 3 Z9 3 U1 0 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2012 VL 19 IS 6 BP 1119 EP 1119 DI 10.1136/amiajnl-2012-001193 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA 028FP UT WOS:000310408500030 PM 22847307 ER PT J AU Bhatia, RS Carne, DM Picard, MH Weiner, RB AF Bhatia, R. Sacha Carne, Dana M. Picard, Michael H. Weiner, Rory B. TI Comparison of the 2007 and 2011 Appropriate Use Criteria for Transthoracic Echocardiography in Various Clinical Settings SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Appropriate use criteria; Transthoracic echocardiography ID CARDIOLOGY FOUNDATION/AMERICAN SOCIETY; OF-CARDIOLOGY; AMERICAN-SOCIETY; HEART-FAILURE; RECOMMENDATIONS; GUIDELINES; DIAGNOSIS; MEDICARE AB Background: The 2007 Appropriate Use Criteria (AUC) for echocardiography was revised in 2011 to cover a wider range of scenarios of use. Previous studies of the 2007 AUC found a relatively large number of unclassified transthoracic echocardiograms (TTEs). Methods: We conducted a retrospective chart review comparing TTE usage in three clinical environments: academic inpatient, academic outpatient, and community outpatient. We assessed the TTE ordering behavior using both the 2007 and 2011 AUC. Results: We reviewed 150 consecutive TTEs performed in 2011 in each of the three practice settings (total 450). Using the 2007 AUC, 347 TTEs (77%) were classifiable, and, using the 2011 AUC, 441 TTEs (98%) were classifiable (P < .001). Of the classified studies, the percentage of appropriate TTEs using the 2007 AUC was 83% and using the 2011 AUC was 71% (P < .001). Using the 2007 and 2011 AUC, the percentage of inappropriate TTEs was 17% and 22% (P = .14), and the percentage of uncertain TTEs was 0% and 7% (P < .001), respectively. The rate of inappropriate studies was greatest in the outpatient academic medical center (30%), followed by the outpatient community health center (21%) and the inpatient academic medical center (14%; P = .004). Conclusions: The 2011 AUC classified a significantly greater proportion of TTEs than the 2007 AUC across a variety of practice settings. The rate of appropriate TTEs was lower using the 2011 AUC, and the appropriateness ratings varied by clinical setting. These findings suggest that the expanded AUC offer an opportunity for improvement in TTE usage. (J Am Soc Echocardiogr 2012;25:1162-9.) C1 [Bhatia, R. Sacha; Carne, Dana M.; Picard, Michael H.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 27 Z9 27 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2012 VL 25 IS 11 BP 1162 EP 1169 DI 10.1016/j.echo.2012.07.018 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 028PC UT WOS:000310433500003 PM 22898245 ER PT J AU Bhatia, RS Carne, DM Picard, MH Weiner, RB AF Bhatia, R. Sacha Carne, Dana M. Picard, Michael H. Weiner, Rory B. TI Comparison of the 2007 and 2011 Appropriate Use Criteria for Transesophageal Echocardiography SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article DE Transesophageal echocardiography; Appropriate use criteria ID TRANSTHORACIC ECHOCARDIOGRAPHY; AMERICAN-SOCIETY; OF-CARDIOLOGY; RECOMMENDATIONS; GUIDELINES; MEDICARE; QUALITY AB Background: The 2007 appropriate use criteria (AUC) for echocardiography were revised in 2011 to cover a wider range of scenarios of use. The aim of this study was to compare the 2011 AUC with the 2007 AUC to determine if the 2011 AUC better classify transesophageal echocardiography (TEE) and to determine the impact of the 2011 AUC on the rates of appropriate and inappropriate TEE at an academic medical center. Methods: A retrospective chart review was conducted to examine inpatient and outpatient TEE utilization. TEE ordering behavior was compared using both the 2007 and 2011 AUC, and studies were classified as appropriate, uncertain, inappropriate, or not classifiable. Results: We reviewed 202 consecutive transesophageal echocardiographic studies (154 inpatient, 48 outpatient) performed in 2011. Using the 2007 AUC, 166 studies (82%) were classifiable, and using the 2011 AUC, 199 (99%) were classifiable (P < .001). Among the classified studies, the percentage of appropriate studies using the 2007 AUC was 94% and using the 2011 AUC was 95% (P = .68). Using 2007 and 2011 AUC, the percentages of inappropriate studies were 0% and 4% (P = .02), and the percentages of uncertain studies were 6% and 1% (P = .006), respectively. Conclusions: The 2011 AUC classify a significantly greater proportion of transesophageal echocardiographic studies than the 2007 AUC. The rate of inappropriate studies using the 2011 AUC is higher than when using the 2007 AUC. These findings suggest that the expanded AUC offer an opportunity for improvement in the utilization of TEE. (J Am Soc Echocardiogr 2012;25:1170-5.) C1 [Bhatia, R. Sacha; Carne, Dana M.; Picard, Michael H.; Weiner, Rory B.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 24 TC 10 Z9 10 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2012 VL 25 IS 11 BP 1170 EP 1175 DI 10.1016/j.echo.2012.07.006 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 028PC UT WOS:000310433500004 PM 22884515 ER PT J AU Wright, CD AF Wright, Cameron D. TI Historical perspectives of The American Association for Thoracic Surgery: John Gordon Scannell (1914-2002) SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, CD (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 2012 VL 144 IS 5 BP 995 EP 997 DI 10.1016/j.jtcvs.2011.03.038 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 025NZ UT WOS:000310197900008 PM 21864853 ER PT J AU Traylor, M Farrall, M Holliday, EG Sudlow, C Hopewell, JC Cheng, YC Fomage, M Ikram, MA Malik, R Bevan, S Thorsteinsdottir, U Nalls, MA Longstreth, WT Wiggins, KL Yadav, S Parati, EA DeStefano, AL Worrall, BB Kittner, S Khan, MS Reiner, AP Helgadottir, A Achterberg, S Fernandez-Cadenas, I Abboud, S Schmidt, R Walters, M Chen, WM Ringelstein, EB O'Donnell, M Ho, WK Pera, J Lemmens, R Norrving, B Higgins, P Benn, M Sale, M Kuhlenbaumer, G Doney, ASF Vicente, AM Delavaran, H Algra, A Davies, G Oliveira, SA Palmer, CNA Deary, I Schmidt, H Pandolfo, M Montaner, J Carty, C de Bakker, PIW Kostulas, K Ferro, JM van Zuydam, NR Valdimarsson, E Nordestgaard, BG Lindgren, A Thijs, V Slowik, A Saleheen, D Pare, G Berger, K Thorleifsson, G Hofman, A Mosley, TH Mitchell, BD Furie, K Clarke, R Levi, C Seshadri, S Gschwendtner, A Boncoraglio, GB Sharma, P Bis, JC Gretarsdottir, S Psaty, BM Rothwell, PM Rosand, J Meschia, JF Stefansson, K Dichgans, M Markus, HS AF Traylor, Matthew Farrall, Martin Holliday, Elizabeth G. Sudlow, Cathie Hopewell, Jemma C. Cheng, Yu-Ching Fomage, Myriam Ikram, M. Arfan Malik, Rainer Bevan, Steve Thorsteinsdottir, Unnur Nalls, Mike A. Longstreth, W. T. Wiggins, Kerri L. Yadav, Sunaina Parati, Eugenio A. DeStefano, Anita L. Worrall, Bradford B. Kittner, Steven Khan, Muhammad Saleem Reiner, Alex P. Helgadottir, Anna Achterberg, Sefanja Fernandez-Cadenas, Israel Abboud, Sherine Schmidt, Reinhold Walters, Matthew Chen, Wei-Min Ringelstein, E. Bernd O'Donnell, Martin Ho, Weang Kee Pera, Joanna Lemmens, Robin Norrving, Bo Higgins, Peter Benn, Marianne Sale, Michele Kuhlenbaeumer, Gregor Doney, Alexander S. F. Vicente, Astrid M. Delavaran, Hossein Algra, Ale Davies, Gail Oliveira, Sofia A. Palmer, Colin N. A. Deary, Ian Schmidt, Helena Pandolfo, Massimo Montaner, Joan Carty, Cara de Bakker, Paul I. W. Kostulas, Konstantinos Ferro, Jose M. van Zuydam, Natalie R. Valdimarsson, Einar Nordestgaard, Borge G. Lindgren, Ame Thijs, Vincent Slowik, Agnieszka Saleheen, Danish Pare, Guillaume Berger, Klaus Thorleifsson, Gudmar Hofman, Albert Mosley, Thomas H. Mitchell, Braxton D. Furie, Karen Clarke, Robert Levi, Christopher Seshadri, Sudha Gschwendtner, Andreas Boncoraglio, Giorgio B. Sharma, Pankaj Bis, Joshua C. Gretarsdottir, Solveig Psaty, Bruce M. Rothwell, Peter M. Rosand, Jonathan Meschia, James F. Stefansson, Kan Dichgans, Martin Markus, Hugh S. CA Australian Stroke Genetics Collabo WTCCC 2 Int Stroke Genetics Consortium TI Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies SO LANCET NEUROLOGY LA English DT Article ID SEQUENCE VARIANTS; LOCI; POPULATION; INFARCTION; DISEASES; COMMON; PRKCH; MAP AB Background Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nudeotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings We verified previous associations for cardioembolic stroke near PITX2 (p=2.8x10(-16)) and ZFHX3 (p=2.28x10(-8)), and for large-vessel stroke at a 9p21 locus (p=3.32x10(-5)) and HDAC9 (p=2.03x10(-12)). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5x10(-6). However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. C1 [Traylor, Matthew; Bevan, Steve; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London SW17 0RE, England. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin; Helgadottir, Anna] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Holliday, Elizabeth G.] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Callaghan, NSW 2308, Australia. [Holliday, Elizabeth G.] Hunter Med Res Inst, Ctr Bioinformat Biomarker Discovery & Informat Ba, Sydney, NSW, Australia. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, Jemma C.; Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Fomage, Myriam] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Ikram, M. Arfan; Hofman, Albert] Erasmus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Ikram, M. Arfan; Hofman, Albert] Consortium Healthy Ageing, Leiden, Netherlands. [Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany. [Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Munich Cluster Syst Neurol SyNergy, Munich, Germany. [Thorsteinsdottir, Unnur; Helgadottir, Anna; Thorleifsson, Gudmar; Gretarsdottir, Solveig; Stefansson, Kan] DeCODE Genet, Reykjavik, Iceland. [Thorsteinsdottir, Unnur; Helgadottir, Anna; Stefansson, Kan] Univ Iceland, Fac Med, Reykjavik, Iceland. [Nalls, Mike A.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA. [Longstreth, W. T.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Longstreth, W. T.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Wiggins, Kerri L.; Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Yadav, Sunaina; Khan, Muhammad Saleem; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, Cerebrovasc Res Unit ICCRU, London, England. [Parati, Eugenio A.; Boncoraglio, Giorgio B.] Ist Neurol Carlo Besta, Fdn Ist Ricovero Cura Carattere Sci IRCCS, Dept Cereberovasc Dis, Milan, Italy. [DeStefano, Anita L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Worrall, Bradford B.; Chen, Wei-Min] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Kittner, Steven] Vet Affairs Med Ctr, Dept Neurol, Baltimore, MA USA. [Kittner, Steven] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Reiner, Alex P.; Carty, Cara] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Achterberg, Sefanja; Algra, Ale] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Neurovasc Res Lab, Dept Neurol, E-08193 Barcelona, Spain. [Fernandez-Cadenas, Israel; Montaner, Joan] Univ Autonoma Barcelona, Dept Med, E-08193 Barcelona, Spain. [Fernandez-Cadenas, Israel; Montaner, Joan] Vall dHebron Hosp, Inst Res, Barcelona, Spain. [Abboud, Sherine; Pandolfo, Massimo] Lab Expt Neurol, Brussels, Belgium. [Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Div Neurogeriatr, Graz, Austria. [Higgins, Peter] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Chen, Wei-Min; Sale, Michele] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Ringelstein, E. Bernd] Univ Munster, Dept Neurol, D-4400 Munster, Germany. [O'Donnell, Martin] Natl Univ Ireland Galway, Galway, Ireland. [Ho, Weang Kee; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Krakow, Poland. [Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Neurobiol Lab, Louvain, Belgium. [Lemmens, Robin; Thijs, Vincent] Univ Leuven KU Leuven, Expt Neurol & Leuven Res Inst Neurodegenerat Dis, Louvain, Belgium. [Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium. [Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Skane Univ Hosp, Dept Neurol, Lund, Sweden. [Norrving, Bo; Delavaran, Hossein; Lindgren, Ame] Lund Univ, Dept Clin Sci Lund, Lund, Sweden. [Benn, Marianne; Nordestgaard, Borge G.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark. [Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Dept Clin Biochem, Copenhagen, Denmark. [Benn, Marianne; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Sale, Michele] Univ Virginia, Dept Internal Med, Div Cardiovasc Med, Charlottesville, VA USA. [Kuhlenbaeumer, Gregor] Univ Kiel, Inst Expt Med, D-24098 Kiel, Germany. [Doney, Alexander S. F.; Palmer, Colin N. A.; van Zuydam, Natalie R.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Vicente, Astrid M.] Inst Natl Sande Dr Ricardo Jorge, Dept Promocao Saude Doencas Cron, Lisbon, Portugal. [Algra, Ale] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. [Davies, Gail; Deary, Ian] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Davies, Gail; Deary, Ian] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Oliveira, Sofia A.] Univ Lisbon, Fac Med, Inst Med Mol, P-1699 Lisbon, Portugal. [Schmidt, Helena] Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.; Rosand, Jonathan] MIT, Cambridge, MA 02139 USA. [de Bakker, Paul I. W.; Rosand, Jonathan] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet, Boston, MA 02115 USA. [Kostulas, Konstantinos] Karolinska Univ Hosp, Karolinska Inst, Dept Neurol, Huddinge, Sweden. [Ferro, Jose M.] Hosp Santa Maria, Ctr Estudos Egas Moniz, Serv Neurol, Lisbon, Portugal. [Valdimarsson, Einar] Univ Hosp, Landspitali, Reykjavik, Iceland. [Nordestgaard, Borge G.] Copenhagen Univ Hosp, Bispebjerg Hosp, Copenhagen City Heart Study, Copenhagen, Denmark. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Pare, Guillaume] McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Pare, Guillaume] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Berger, Klaus] Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. [Mosley, Thomas H.; Rosand, Jonathan] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Furie, Karen] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Levi, Christopher] Univ Newcastle, Ctr Translat Neurosci & Mental Hlth Res, New Lambton, NSW, Australia. [Levi, Christopher] Hunter Med Res Inst, New Lambton, NSW, Australia. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Dept Med, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Seattle, Grp Hlth Res Inst, Seattle, WA USA. [Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. RP Markus, HS (reprint author), St Georges Univ London, Stroke & Dementia Res Ctr, Cranmer Terrace, London SW17 0RE, England. EM hmarkus@sgul.ac.uk RI Palmer, Colin/C-7053-2008; Vicente, Astrid/F-8692-2014; Thijs, Vincent/C-3647-2009; Carty, Cara/B-8683-2013; Deary, Ian/C-6297-2009; de Bakker, Paul/B-8730-2009; Boncoraglio, Giorgio/B-8647-2011; Montaner, Joan/D-3063-2015; IBIS, NEUROVASCULAR/O-1855-2015; Study, GoDARTS/K-9448-2016; OI O'Donnell, Martin/0000-0002-7347-7761; Norrving, Bo/0000-0002-8024-5096; HO, WEANG KEE/0000-0002-8269-7344; Ikram, Mohammad Arfan/0000-0003-0372-8585; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Ferro, Jose/0000-0002-2343-9097; Mitchell, Braxton/0000-0003-4920-4744; Seshadri, Sudha/0000-0001-6135-2622; Palmer, Colin/0000-0002-6415-6560; Vicente, Astrid/0000-0001-7134-8037; Thijs, Vincent/0000-0002-6614-8417; de Bakker, Paul/0000-0001-7735-7858; Oliveira, Sofia A/0000-0001-7919-4191; Benn, Marianne/0000-0002-1701-595X FU Wellcome Trust; UK Medical Research Council (MRC); Australian National and Medical Health Research Council; National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI); National Institute on Aging (NIA); National Human Genome Research Institute (NHGRI); National Institute of Neurological Disorders and Stroke (NINDS); National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C]; NHLBI [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01-HL087641, U01 HL096917, R01-HL093029, N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129]; NIH Roadmap for Medical Research [UL1RR025005]; METASTROKE project [HL-093029]; University of Newcastle; Australian National and Medical Health Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; Gladys M Brawn Fellowship; Vincent Fairfax Family Foundation in Australia; Australian NHMRC Fellowship; Department of Health (UK); Henry Smith Charity; UK-India Education Research Institutive (UKIERI) from the British Council; National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; National Center of Advancing Translational Technologies CTSI [UL1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; European Community [HEALTH-F4-2007-201413]; Framingham Heart Study; NHLBI's Framingham Heart Study [N01-HC-25195, N02-HL-6-4278]; NINDS [NS17950]; NIA [AG033193]; NIH Genes; Almirall; Astra Zeneca; Berlin Chemie; Boehringer; Boots Health Care; Glaxo-Smith-Kline; Janssen Cilag; McNeil Pharma; MSD Sharp Dohme; Pfizer; Portuguese Fundacao para a Ciencia e a Tecnologia; Jagiellonian University, Krakow Poland [K/ZDS/002848]; Netherlands Heart Foundation [2005B031]; United States National Human Genome Research Institute (NHGRI) as part of the Genomics and Randomized Trials Network (GARNET) [U01 HG005160]; NIH; GARNET Coordinating Center [U01 HG005157]; United States Public Health Service, NINDS, Bethesda, Maryland [R01 NS34447]; United States National Center for Biotechnology Information, US National Library of Medicine; WHI-GARNET through the NHGRI GARNET [U01 HG005152]; NIH Genes, Environment, and Health Initiative [U01 HG004424]; National Heart, Lung and Blood Institute [N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C, HL080295, HL087652, HL105756, HL93029]; [PTDC/SAU-GMG/64426/2006] FX Funding Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS).; Atherosclerosis Risk in Communities Study (ARIC) is a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; National Institutes of Health (NIH) contract HHSN268200625226C; and NHLBI contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, and grants R01-HL087641, U01 HL096917 (T H Mosley), and R01-HL093029 (M Fornage). Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. ARIC analyses performed as part of the METASTROKE project were supported by grant HL-093029 to M Fornage. Australian Stroke Genetics Collaboration (ASGC) Australian population control data were derived from the Hunter Community Study. We also thank the University of Newcastle for funding and the men and women of the Hunter region who participated in this study. This research was funded by grants from the Australian National and Medical Health Research Council (NHMRC Project Grant ID: 569257), the Australian National Heart Foundation (NHF Project Grant ID: G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme, and the Vincent Fairfax Family Foundation in Australia. Elizabeth G Holliday is supported by the Australian NHMRC Fellowship scheme. Bio-Repository of DNA in Stroke (BRAINS) is partly funded by a Senior Fellowship from the Department of Health (UK) to P Sharma, the Henry Smith Charity and the UK-India Education Research Institutive (UKIERI) from the British Council. Cardiovascular Health Study (CHS) research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HHSN268201200036C and NHLBI grants HL080295, HL087652, HL105756 with additional contribution from the National Institute of Neurological Diseases and Stroke (NINDS). Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA). DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies CTSI grant UL1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. deCODE Genetics Work performed at deCODE was funded in part through a grant from the European Community's Seventh Framework Programme (FP7/2007-2013), the ENGAGE project grant agreement HEALTH-F4-2007-201413. Framingham Heart Study (FHS) This work was supported by the dedication of the Framingham Heart Study participants, the NHLBI's Framingham Heart Study (Contract Nos. N01-HC-25195 and N02-HL-6-4278), and by grants from the NINDS (NS17950), the NHLBI (HL93029), and the NIA (AG033193). Genetics of Early Onset Stroke (GEOS) Study, Baltimore, USA was supported by the NIH Genes, grants of equal share from Almirall, Astra Zeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp & Dohme, and Pfizer to the University of Muenster. Portugal SAO, JMF, and AMV are deeply grateful to all study participants, to the genotyping unit at the Instituto Gulbenkian de Ciencia, and to the Portuguese study neurologists and nurses for their contributions.; This work was supported by the PTDC/SAU-GMG/64426/2006 grant, a Cilencia 2008 contract (SAO) and doctoral fellowships from the Portuguese Fundacao para a Ciencia e a Tecnologia. Poland: Krakow The study was supported by the grant from the Jagiellonian University, Krakow Poland: K/ZDS/002848. SMART-study the Netherlands Genotyping in the SMART Study was made possible, in part, by a Complementation Grant to P I W de Bakker from the Biobanking and Biomolecular Research Infrastructure in the Netherlands (BBMRI-NL). S Achterberg is working in part on a grant from the Netherlands Heart Foundation, No. 2005B031. VISP The GWAS component of the VISP study was supported by the United States National Human Genome Research Institute (NHGRI), Grant U01 HG005160 (PI Michele Sale & Bradford Worrell), as part of the Genomics and Randomized Trials Network (GARNET). Genotyping services were provided by the Johns Hopkins University Center for Inherited Disease Research (CIDR), which is fully funded through a federal contract from the NIH to the Johns Hopkins University. Assistance with data cleaning was provided by the GARNET Coordinating Center (U01 HG005157; PI Bruce S Weir). Study recruitment and collection of datasets for the VISP clinical trial were supported by an investigator-initiated research grant (R01 NS34447; PI James Toole) from the United States Public Health Service, NINDS, Bethesda, Maryland. Control data obtained through the database of genotypes and phenotypes (dbGAP) maintained and supported by the United States National Center for Biotechnology Information, US National Library of Medicine. W H I Funding support for WHI-GARNET was provided through the NHGRI GARNET (Grant Number U01 HG005152). Assistance with phenotype harmonisation and genotype cleaning, as well as with general study coordination, was provided by the GARNET Coordinating Center (U01 HG005157). Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard, was provided by the NIH Genes, Environment, and Health Initiative (GEI; U01 HG004424). NR 31 TC 179 Z9 189 U1 3 U2 37 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 EI 1474-4465 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2012 VL 11 IS 11 BP 951 EP 962 DI 10.1016/S1474-4422(12)70234-X PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 028KW UT WOS:000310422200011 PM 23041239 ER PT J AU Assis, L Moretti, AIS Abrahao, TB Cury, V Souza, HP Hamblin, MR Parizotto, NA AF Assis, Livia Moretti, Ana I. S. Abrahao, Thalita B. Cury, Vivian Souza, Heraldo P. Hamblin, Michael R. Parizotto, Nivaldo A. TI Low-level laser therapy (808 nm) reduces inflammatory response and oxidative stress in rat tibialis anterior muscle after cryolesion SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE low-level laser therapy; photobiomodulation; muscle cryolesion; inflammatory mediators; nitrative stress; oxidative stress ID NF-KAPPA-B; SKELETAL-MUSCLE; NITRIC-OXIDE; TRANSCRIPTION FACTOR; IN-VITRO; IRRADIATION; INJURY; REGENERATION; EXPRESSION; REPAIR AB Background and Objective Muscle regeneration is a complex phenomenon, involving coordinated activation of several cellular responses. During this process, oxidative stress and consequent tissue damage occur with a severity that may depend on the intensity and duration of the inflammatory response. Among the therapeutic approaches to attenuate inflammation and increase tissue repair, low-level laser therapy (LLLT) may be a safe and effective clinical procedure. The aim of this study was to evaluate the effects of LLLT on oxidative/nitrative stress and inflammatory mediators produced during a cryolesion of the tibialis anterior (TA) muscle in rats. Material and Methods Sixty Wistar rats were randomly divided into three groups (n?=?20): control (BC), injured TA muscle without LLLT (IC), injured TA muscle submitted to LLLT (IRI). The injured region was irradiated daily for 4 consecutive days, starting immediately after the lesion using a AlGaAs laser (continuous wave, 808?nm, tip area of 0.00785?cm2, power 30?mW, application time 47?seconds, fluence 180?J/cm2; 3.8?mW/cm2; and total energy 1.4?J). The animals were sacrificed on the fourth day after injury. Results LLLT reduced oxidative and nitrative stress in injured muscle, decreased lipid peroxidation, nitrotyrosine formation and NO production, probably due to reduction in iNOS protein expression. Moreover, LLLT increased SOD gene expression, and decreased the inflammatory response as measured by gene expression of NF-k beta and COX-2 and by TNF-a and IL-1 beta concentration. Conclusion These results suggest that LLLT could be an effective therapeutic approach to modulate oxidative and nitrative stress and to reduce inflammation in injured muscle. Lasers Surg. Med. 44: 726735, 2012. (c) 2012 Wiley Periodicals, Inc. C1 [Moretti, Ana I. S.] Univ Sao Paulo, Fac Med, Emergency Med Div, Lab Med Res, BR-01246903 Sao Paulo, Brazil. [Assis, Livia; Cury, Vivian; Parizotto, Nivaldo A.] Univ Sao Paulo, Dept Phisiotherapy, Lab Electrothermophototherapy, Sao Carlos, SP, Brazil. [Moretti, Ana I. S.] Inst Assistencia Med Servidor Publ Estadual IAMSP, Postgrad Hlth Sci Program, Sao Paulo, Brazil. [Abrahao, Thalita B.] Univ Sao Paulo, Fac Med, Lab Vasc Biol, Dept Cardiopneumol,Heart Inst, BR-01246903 Sao Paulo, Brazil. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Moretti, AIS (reprint author), Univ Sao Paulo, Fac Med, Emergency Med Div, Lab Med Res, Brazil Av Dr Arnaldo 455,Sala 3189, BR-01246903 Sao Paulo, Brazil. EM aismoretti@yahoo.com.br RI PARIZOTTO, Nivaldo/D-5347-2014; Assis, Livia/H-8299-2012; moretti, ana/J-9064-2012; Cury, Vivian/O-4405-2015; Souza, Heraldo/C-2498-2012; OI PARIZOTTO, Nivaldo/0000-0003-1774-9053; Assis, Livia/0000-0002-8343-3375; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Emergency Medicine Division [LIM 51]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2006/01096-8, 2009/01990-9]; Conselho Nacional de Desenvolvimento Cientifico (CNPQ) [473537/2008-7, 151747/2007-5]; CAPES; CNPQ; FAPESP FX Contract grant sponsor: NIH; Contract grant number: R01AI050875; Contract grant sponsor: Emergency Medicine Division; Contract grant number: LIM 51; Contract grant sponsor: Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Contract grant number: 2006/01096-8, 2009/01990-9; Contract grant sponsor: Conselho Nacional de Desenvolvimento Cientifico (CNPQ); Contract grant number: 473537/2008-7, 151747/2007-5.; We acknowledge CAPES, CNPQ and FAPESP for financial support. M. R. Hamblin was supported by NIH (grant R01AI050875). Emergency Medicine Division (LIM 51), Faculdade de Medicina da Universidade de Sao Paulo to provide technical support in biochemical and molecular biology analyses and NUPEN (Nucleo de Pesquisa e Ensino em Fototerapia nas Ciencias da Saude) for supporting and calibrating the laser equipment. NR 43 TC 47 Z9 48 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD NOV PY 2012 VL 44 IS 9 BP 726 EP 735 DI 10.1002/lsm.22077 PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 026AF UT WOS:000310239400005 PM 23001637 ER PT J AU Gellad, WF Aspinall, SL Handler, SM Stone, RA Castle, N Semla, TP Good, CB Fine, MJ Dysken, M Hanlon, JT AF Gellad, Walid F. Aspinall, Sherrie L. Handler, Steven M. Stone, Roslyn A. Castle, Nicholas Semla, Todd P. Good, Chester B. Fine, Michael J. Dysken, Maurice Hanlon, Joseph T. TI Use of Antipsychotics Among Older Residents in VA Nursing Homes SO MEDICAL CARE LA English DT Article DE nursing homes; antipsychotics; Veterans; pharma-coepidemiology ID DRUG-USE; MEDICATION USE; PRESCRIBING RATES; CONTROLLED-TRIAL; DEMENTIA; VETERANS; METAANALYSIS; CARE; PARKINSONISM; POLYPHARMACY AB Background: Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Affairs (VA) nursing homes [ie, Community Living Centers (CLCs)], we assessed the prevalence and risk factors for antipsychotic use in older residents of VA CLCs. Methods: This cross-sectional study included 3692 Veterans age 65 or older who were admitted between January 2004 and June 2005 to one of 133 VA CLCs and had a stay of >= 90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (eg, schizophrenia, dementia with psychosis). We used multivariable logistic regression and generalized estimating equations to identify factors independently associated with antipsychotic receipt. Results: Overall, 948/3692(25.7%) residents received an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior [odds ratio (OR) = 2.74, 95% confidence interval (CI), 2.04-3.67] and polypharmacy (9+ drugs; OR = 1.84, 95% CI, 1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR = 1.37, 95% CI, 1.14-1.66), anxiolytic/hypnotics (OR = 2.30, 95% CI, 1.64-3.23), or drugs for dementia (OR = 1.52, 95% CI, 1.21-1.92). Those residing in Alzheimer/dementia special care units were also more likely to receive an antipsychotic (OR = 1.66, 95% CI, 1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR = 1.10, 95% CI, 0.82-1.47). Conclusions: Antipsychotic use is common among VA nursing home residents aged 65 and older, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing. C1 [Gellad, Walid F.; Aspinall, Sherrie L.; Handler, Steven M.; Stone, Roslyn A.; Good, Chester B.; Fine, Michael J.; Hanlon, Joseph T.] VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15206 USA. [Gellad, Walid F.; Good, Chester B.; Fine, Michael J.] Univ Pittsburgh, Dept Med Gen Med, Pittsburgh, PA USA. [Gellad, Walid F.; Aspinall, Sherrie L.; Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Geriatr Pharmaceut & Geroinformat Res & Training, Pittsburgh, PA USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Semla, Todd P.; Good, Chester B.] US Dept Vet Affairs, Pharm Benefits Management Serv, Hines, IL USA. [Aspinall, Sherrie L.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Handler, Steven M.] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA. [Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Pittsburgh VA Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Handler, Steven M.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Med Geriatr, Pittsburgh, PA USA. [Stone, Roslyn A.; Castle, Nicholas] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Semla, Todd P.] Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Psychiat, Chicago, IL 60611 USA. [Semla, Todd P.] Northwestern Univ, Feinberg Sch Med, Dept Behav Sci, Chicago, IL 60611 USA. [Dysken, Maurice; Hanlon, Joseph T.] Minneapolis VA Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA. RP Gellad, WF (reprint author), VA Pittsburgh Hlthcare Syst, Ctr Hlth Equity Res & Promot, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM walid.gellad@va.gov OI Handler, Steven/0000-0002-3940-3224 FU VA Career Development Award [CDA 09-207]; National Institute of Aging [P30AG024827, T32 AG021885, K07AG033174, R01AG034056, R56AG027017, 3U01 AG012553]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [R01 HS017695, R01 HS018721, K12 HS019461] FX Supported by a VA Career Development Award (CDA 09-207), National Institute of Aging Grants (P30AG024827, T32 AG021885, K07AG033174, R01AG034056, R56AG027017, 3U01 AG012553), a National Institute of Mental Health Grant (R34 MH082682), a National Institute of Nursing Research grant (R01 NR010135), and Agency for Healthcare Research and Quality Grants (R01 HS017695, R01 HS018721, K12 HS019461). NR 49 TC 24 Z9 24 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD NOV PY 2012 VL 50 IS 11 BP 954 EP 960 DI 10.1097/MLR.0b013e31825fb21d PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 022OL UT WOS:000309968600009 PM 23047785 ER PT J AU Zhu, ZL Massimini, DF Wang, GZ Warner, JJP Li, GA AF Zhu, Zhonglin Massimini, Daniel F. Wang, Guangzhi Warner, Jon J. P. Li, Guoan TI The accuracy and repeatability of an automatic 2D-3D fluoroscopic image-model registration technique for determining shoulder joint kinematics SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Optimization; Single plane; Dual plane; Biplane ID IN-VIVO MEASUREMENT; PROFESSIONAL BASEBALL PITCHERS; ARTICULAR-CARTILAGE CONTACT; GLENOHUMERAL TRANSLATION; SCAPULOHUMERAL RHYTHM; SCAPULAR KINEMATICS; MATCHING METHOD; MOTION; ELEVATION; VALIDATION AB Fluoroscopic imaging, using single plane or dual plane images, has grown in popularity to measure dynamic in vivo human shoulder joint kinematics. However, no study has quantified the difference in spatial positional accuracy between single and dual plane image-model registration applied to the shoulder joint. In this paper, an automatic 2D-3D image-model registration technique was validated for accuracy and repeatability with single and dual plane fluoroscopic images. Accuracy was assessed in a cadaver model, kinematics found using the automatic registration technique were compared to those found using radiostereometric analysis. The in vivo repeatability of the automatic registration technique was assessed during the dynamic abduction motion of four human subjects. The in vitro data indicated that the error in spatial positional accuracy of the humerus and the scapula was less than 0.30 mm in translation and less than 0.58 degrees in rotation using dual plane images. Single plane accuracy was satisfactory for in-plane motion variables, but out-of-plane motion variables on average were approximately 8 times less accurate. The in vivo test indicated that the repeatability of the automatic 2D-3D image-model registration was 0.50 mm in translation and 1.04 degrees in rotation using dual images. For a single plane technique, the repeatability was 3.31 mm in translation and 2.46 degrees in rotation for measuring shoulder joint kinematics. The data demonstrate that accurate and repeatable shoulder joint kinematics can be obtained using dual plane fluoroscopic images with an automatic 2D-3D image-model registration technique; and that out-of-plane motion variables are less accurate than in-plane motion variables using a single plane technique. (C) 2012 IPEM. Published by Elsevier Ltd. All rights reserved. C1 [Zhu, Zhonglin; Wang, Guangzhi] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Zhu, Zhonglin; Massimini, Daniel F.; Warner, Jon J. P.; Li, Guoan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Massimini, Daniel F.] MIT, Dept Mech Engn, Boston, MA USA. RP Li, GA (reprint author), Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM zhonglinzhu@gmail.com; dmass@mit.edu; gli1@partners.org OI Wang, Guangzhi/0000-0002-4677-1041 FU Harvard Shoulder Service at the Massachusetts General Hospital; National Program on Key Basic Research Project [2011CB707701]; National Key Technologies R & D Program of China [2011BAF01B03] FX This study was partially supported by the Harvard Shoulder Service at the Massachusetts General Hospital, a grant from National Program on Key Basic Research Project (2011CB707701) and a grant from National Key Technologies R & D Program of China (2011BAF01B03). NR 42 TC 20 Z9 20 U1 0 U2 21 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD NOV PY 2012 VL 34 IS 9 BP 1303 EP 1309 DI 10.1016/j.medengphy.2011.12.021 PG 7 WC Engineering, Biomedical SC Engineering GA 028LH UT WOS:000310423300012 PM 22285714 ER PT J AU Mochida, GH Ganesh, VS de Michelena, MI Dias, H Atabay, KD Kathrein, KL Huang, HT Hill, RS Felie, JM Rakiec, D Gleason, D Hill, AD Malik, AN Barry, BJ Partlow, JN Tan, WH Glader, LJ Barkovich, AJ Dobyns, WB Zon, LI Walsh, CA AF Mochida, Ganeshwaran H. Ganesh, Vijay S. de Michelena, Maria I. Dias, Hugo Atabay, Kutay D. Kathrein, Katie L. Huang, Hsuan-Ting Hill, R. Sean Felie, Jillian M. Rakiec, Daniel Gleason, Danielle Hill, Anthony D. Malik, Athar N. Barry, Brenda J. Partlow, Jennifer N. Tan, Wen-Hann Glader, Laurie J. Barkovich, A. James Dobyns, William B. Zon, Leonard I. Walsh, Christopher A. TI CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development SO NATURE GENETICS LA English DT Article ID PROLIFERATION; POPULATION; PROTEINS; MATRIX; BMI1 AB Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex(1,2) but is also suggested to localize to the nuclear matrix and regulate chromatin structure(3). Here, we show that loss-of-function mutations in human CHMP1A cause reduced cerebellar size (pontocerebellar hypoplasia) and reduced cerebral cortical size (microcephaly). CHMP1A-mutant cells show impaired proliferation, with increased expression of INK4A, a negative regulator of stem cell proliferation. Chromatin immunoprecipitation suggests loss of the normal INK4A repression by BMI in these cells. Morpholino-based knockdown of zebrafish chmp1a resulted in brain defects resembling those seen after bmi1a and bmi1b knockdown, which were partially rescued by INK4A ortholog knockdown, further supporting links between CHMP1A and BMI1-mediated regulation of INK4A. Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells. C1 [Mochida, Ganeshwaran H.; Ganesh, Vijay S.; Atabay, Kutay D.; Hill, R. Sean; Felie, Jillian M.; Rakiec, Daniel; Gleason, Danielle; Barry, Brenda J.; Partlow, Jennifer N.; Tan, Wen-Hann; Walsh, Christopher A.] Boston Childrens Hosp, Div Genet, Dept Med, Boston, MA USA. [Mochida, Ganeshwaran H.; Ganesh, Vijay S.; Atabay, Kutay D.; Hill, R. Sean; Felie, Jillian M.; Rakiec, Daniel; Gleason, Danielle; Barry, Brenda J.; Partlow, Jennifer N.; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA USA. [Mochida, Ganeshwaran H.; Ganesh, Vijay S.; Atabay, Kutay D.; Kathrein, Katie L.; Huang, Hsuan-Ting; Hill, R. Sean; Felie, Jillian M.; Rakiec, Daniel; Gleason, Danielle; Barry, Brenda J.; Partlow, Jennifer N.; Zon, Leonard I.; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA USA. [Mochida, Ganeshwaran H.; Tan, Wen-Hann; Glader, Laurie J.; Zon, Leonard I.; Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Mochida, Ganeshwaran H.] Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. [Ganesh, Vijay S.; Malik, Athar N.] Harvard Massachusetts Inst Technol MIT Div Hlth S, Cambridge, MA USA. [de Michelena, Maria I.] Cayetano Heredia Univ, Dept Morphol Sci, Lima, Peru. [Dias, Hugo] Inst Child Dev ARIE, Lima, Peru. [Kathrein, Katie L.; Huang, Hsuan-Ting; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA USA. [Kathrein, Katie L.; Huang, Hsuan-Ting; Zon, Leonard I.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Kathrein, Katie L.; Huang, Hsuan-Ting; Zon, Leonard I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hill, Anthony D.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Glader, Laurie J.] Boston Childrens Hosp, Div Gen Pediat, Complex Care Serv, Boston, MA USA. [Barkovich, A. James] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Dobyns, William B.] Univ Washington, Ctr Integrat Brain Res, Seattle, WA 98195 USA. [Zon, Leonard I.] Harvard Stem Cell Inst, Cambridge, MA USA. [Walsh, Christopher A.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Walsh, CA (reprint author), Boston Childrens Hosp, Div Genet, Dept Med, Boston, MA USA. EM christopher.walsh@childrens.harvard.edu OI Dobyns, William/0000-0002-7681-2844 FU US National Institute of Neurological Disorders and Stroke (NINDS) [R01NS035129]; Fogarty International Center [R21TW008223]; Dubai Harvard Foundation for Medical Research; Simons Foundation; Manton Center for Orphan Disease Research; National Alliance for Research on Schizophrenia and Depression (NARSAD); Harvard Medical School; US National institute of General Medical Sciences (NIGMS) FX We thank the individuals and their families reported herein for their participation in this research. We thank M. van Lohuizen (Netherlands Cancer Institute) for providing the Bmi1-knockout mice, A. Wagers for help with breeding the Bmi1-knockout mice and P. Baas for sharing human DNA samples. This research was supported by grants from the US National Institute of Neurological Disorders and Stroke (NINDS; R01NS035129) and the Fogarty International Center (R21TW008223) to C.A.W, the Dubai Harvard Foundation for Medical Research, the Simons Foundation and the Manton Center for Orphan Disease Research. G.H.M. was supported by the Young Investigator Award of the National Alliance for Research on Schizophrenia and Depression (NARSAD) as a NARSAD Lieber Investigator. V.S.G. is supported by the Medical Scientist Training Program of Harvard Medical School, with financial support from the US National institute of General Medical Sciences (NIGMS). C.A.W and L.I.Z. are investigators of the Howard Hughes Medical Institute. Microscopy and image analyses were performed with support from the Cellular Imaging Core of the Boston Children's Hospital Intellectual and Developmental Disabilities Research Center. NR 12 TC 27 Z9 29 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2012 VL 44 IS 11 BP 1260 EP 1264 DI 10.1038/ng.2425 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 029KZ UT WOS:000310495800020 PM 23023333 ER PT J AU Pitman, RK Rasmusson, AM Koenen, KC Shin, LM Orr, SP Gilbertson, MW Milad, MR Liberzon, I AF Pitman, Roger K. Rasmusson, Ann M. Koenen, Karestan C. Shin, Lisa M. Orr, Scott P. Gilbertson, Mark W. Milad, Mohammed R. Liberzon, Israel TI Biological studies of post-traumatic stress disorder SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SINGLE-PROLONGED STRESS; CHILDHOOD SEXUAL-ABUSE; CORTICOTROPIN-RELEASING-FACTOR; ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; SEROTONIN TRANSPORTER GENOTYPE; MONOZYGOTIC TWINS DISCORDANT; AUDITORY STARTLE RESPONSE; INTIMATE PARTNER VIOLENCE AB Post-traumatic stress disorder (PTSD) is the only major mental disorder for which a cause is considered to be known: that is, an event that involves threat to the physical integrity of oneself or others and induces a response of intense fear, helplessness or horror. Although PTSD is still largely regarded as a psychological phenomenon, over the past three decades the growth of the biological PTSD literature has been explosive, and thousands of references now exist. Ultimately, the impact of an environmental event, such as a psychological trauma, must be understood at organic, cellular and molecular levels. This Review attempts to present the current state of this understanding on the basis of psychophysiological, structural and functional neuroimaging, and endocrinological, genetic and molecular biological studies in humans and in animal models. C1 [Pitman, Roger K.; Shin, Lisa M.; Orr, Scott P.; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Pitman, Roger K.; Orr, Scott P.; Gilbertson, Mark W.; Milad, Mohammed R.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rasmusson, Ann M.] Vet Affairs Boston Healthcare Syst, Boston, MA 02130 USA. [Rasmusson, Ann M.] Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Rasmusson, Ann M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. [Shin, Lisa M.] Tufts Univ, Dept Psychol, Boston, MA 02155 USA. [Gilbertson, Mark W.] Vet Affairs Med Ctr, Res Serv, Manchester, NH 03104 USA. [Gilbertson, Mark W.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Liberzon, Israel] Vet Affairs Med Ctr, Psychiat Serv, Ann Arbor, MI 48105 USA. [Liberzon, Israel] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48103 USA. RP Pitman, RK (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM roger_pitman@hms.harvard.edu RI Koenen, Karestan/K-5402-2014; OI Koenen, Karestan/0000-0003-3293-4281; Liberzon, Israel/0000-0002-4990-556X FU NIMH NIH HHS [R01 MH081975] NR 222 TC 282 Z9 284 U1 31 U2 175 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD NOV PY 2012 VL 13 IS 11 BP 769 EP 787 DI 10.1038/nrn3339 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 027ME UT WOS:000310355700010 PM 23047775 ER PT J AU Quayle, SN Chheda, MG Shukla, SA Wiedemeyer, R Tamayo, P Dewan, RW Zhuang, L Huang-Hobbs, E Haidar, S Xiao, YH Ligon, KL Hahn, WC Chin, L AF Quayle, Steven N. Chheda, Milan G. Shukla, Sachet A. Wiedemeyer, Ruprecht Tamayo, Pablo Dewan, Robert W. Zhuang, Li Huang-Hobbs, Emmet Haidar, Sam Xiao, Yonghong Ligon, Keith L. Hahn, William C. Chin, Lynda TI Integrative functional genomics identifies RINT1 as a novel GBM oncogene SO NEURO-ONCOLOGY LA English DT Article DE functional genomics; glioblastoma; oncogene; oncogenomics ID RAD50-INTERACTING PROTEIN; TUMOR-SUPPRESSOR; GLIOBLASTOMA; CANCERS; GENES; BREAST; GLIOMA AB Large-scale cancer genomics efforts are identifying hundreds of somatic genomic alterations in glioblastoma (GBM). Distinguishing between active driver and neutral passenger alterations requires functional assessment of each gene; therefore, integrating biological weight of evidence with statistical significance for each genomic alteration will enable better prioritization for downstream studies. Here, we demonstrate the feasibility and potential of in vitro functional genomic screens to rapidly and systematically prioritize high-probability candidate genes for in vivo validation. Integration of low-complexity gain- and loss-of-function screens designed on the basis of genomic data identified 6 candidate GBM oncogenes, and RINT1 was validated as a novel GBM oncogene based on its ability to confer tumorigenicity to primary nontransformed murine astrocytes in vivo. Cancer genomics-guided low-complexity genomic screens can quickly provide a functional filter to prioritize high-value targets for further downstream mechanistic and translational studies. C1 [Quayle, Steven N.; Chheda, Milan G.; Shukla, Sachet A.; Wiedemeyer, Ruprecht; Dewan, Robert W.; Zhuang, Li; Huang-Hobbs, Emmet; Haidar, Sam; Xiao, Yonghong; Ligon, Keith L.; Hahn, William C.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Shukla, Sachet A.; Xiao, Yonghong; Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Appl Canc Sci, Boston, MA 02115 USA. [Tamayo, Pablo; Hahn, William C.; Chin, Lynda] Broad Inst Harvard & MIT, Cambridge, MA USA. [Hahn, William C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Chin, L (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Genom Med, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU Canadian Institutes of Health Research; National Institutes of Health [K08NS062907, K12CA090354, PO1CA095616, U01CA141508, U24CA143845, RC2CA148268]; AACR-NBTF Fellowship in memory of Bonnie Brooks; Trudy Bettiker/American Brain Tumor Foundation Fellowship; Ben and Catherine Ivy Foundation; Snyder Medical Foundation; Sontag Foundation; Goldhirsh Foundation FX S. N. Q. was supported by a fellowship from the Canadian Institutes of Health Research. M. G. C. was supported by National Institutes of Health grants K08NS062907 and K12CA090354, an AACR-NBTF Fellowship in memory of Bonnie Brooks, and a Trudy Bettiker/American Brain Tumor Foundation Fellowship. L. C., W. C. H., and K. L. L. are supported by grants from the Ben and Catherine Ivy Foundation, the Snyder Medical Foundation, the Sontag Foundation, the Goldhirsh Foundation, and National Institutes of Health grants PO1CA095616, U01CA141508, U24CA143845, and RC2CA148268. NR 19 TC 8 Z9 8 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2012 VL 14 IS 11 BP 1325 EP 1331 DI 10.1093/neuonc/nos246 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 027SN UT WOS:000310373800003 PM 23074196 ER PT J AU Budson, AE Solomon, PR AF Budson, Andrew E. Solomon, Paul R. TI New Criteria for Alzheimer Disease and Mild Cognitive Impairment Implications for the Practicing Clinician SO NEUROLOGIST LA English DT Review DE Alzheimer disease; AD; mild cognitive impairment; MCI; criteria; preclinical ID ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; RECOMMENDATIONS; DEMENTIA; PREVALENCE AB Background: In most research studies and clinical trials, Alzheimer disease (AD) has been diagnosed using the criteria developed by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association work group in 1984. Developments over the last 27 years have lead to the need for new diagnostic criteria. Review Summary: Four articles in the journal Alzheimer's & Dementia in 2011 describe new criteria for AD dementia and mild cognitive impairment (MCI) due to the AD pathophysiological process (MCI due to AD) and the underlying rationale for them. These new criteria emphasize that the AD pathophysiological process starts years and perhaps decades before clinical symptoms, and that biomarkers can be used to detect amyloid beta deposition and the effects of neurodegeneration in the brain. Conclusions: These new criteria are immediately helpful to the practicing clinician, providing more accurate and specific guidelines for the diagnosis of AD dementia and MCI due to AD. As new diagnostic tools and new treatments for AD become available, diagnosis using these criteria will enable patients with this disorder to receive the best possible care. C1 [Budson, Andrew E.] VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, Boston, MA 02132 USA. [Budson, Andrew E.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Solomon, Paul R.] Williams Coll, Program Neurosci, Dept Psychol, Williamstown, MA 01267 USA. [Budson, Andrew E.; Solomon, Paul R.] Memory Clin, Bennington, VT USA. RP Budson, AE (reprint author), VA Boston Healthcare Syst, Ctr Translat Cognit Neurosci, 1400 VFW Pkwy, Boston, MA 02132 USA. EM abudson@bu.edu FU National Institute on Aging [P30 AG13846] FX Supported by National Institute on Aging grant P30 AG13846. This material is also the result of work supported with resources and the use of facilities at the VA Boston Healthcare System. NR 14 TC 7 Z9 9 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2012 VL 18 IS 6 BP 356 EP 363 DI 10.1097/NRL.0b013e31826a998d PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 031HA UT WOS:000310628800004 PM 23114667 ER PT J AU Yamasaki, A Booker, A Kapur, V Tilt, A Niess, H Lillemoe, KD Warshaw, AL Conrad, C AF Yamasaki, Alisa Booker, Abigail Kapur, Varun Tilt, Alexandra Niess, Hanno Lillemoe, Keith D. Warshaw, Andrew L. Conrad, Claudius TI The impact of music on metabolism SO NUTRITION LA English DT Review DE Music; Metabolism; Music therapy; Hypothalamic-pituitary axis; Sympathetic nervous system; Immune system; Stress; Pain management; Neonatal metabolism; Gastric physiology; Gastric myoelectrical activity; Exercise metabolism ID GASTRIC MYOELECTRICAL ACTIVITY; HEART-RATE-VARIABILITY; ENERGY-EXPENDITURE; STRESS; THERAPY; RESPONSES; MEDICINE; HORMONE; MICE; INTERLEUKIN-6 AB The study of music and medicine is a rapidly growing field that in the past, has been largely focused on the use of music as a complementary therapy. Increasing interest has been centered on understanding the physiologic mechanisms underlying the effects of music and, more recently, the suggested role of music in modulating metabolic responses. Research has established a role for music in the regulation of the hypothalamic-pituitary axis, the sympathetic nervous system, and the immune system, which have key functions in the regulation of metabolism and energy balance. More recent findings have shown a role for music in the metabolic recovery from stress, the regulation of gastric and intestinal motility, the moderation of cancer-related gastrointestinal symptoms, and the increase of lipid metabolism and lactic acid clearance during exercise and postexercise recovery. The purpose of this article is to summarize the most current understanding of the mechanisms by which music affects the metabolic responses in the context of potential applications. (C) 2012 Elsevier Inc. All rights reserved. C1 [Yamasaki, Alisa; Booker, Abigail; Kapur, Varun; Tilt, Alexandra; Lillemoe, Keith D.; Warshaw, Andrew L.; Conrad, Claudius] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Booker, Abigail; Tilt, Alexandra] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Niess, Hanno] Univ Munich Grosshadem, Dept Surg, Munich, Germany. RP Conrad, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM cconrad1@partners.org NR 48 TC 8 Z9 10 U1 5 U2 71 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD NOV-DEC PY 2012 VL 28 IS 11-12 BP 1075 EP 1080 DI 10.1016/j.nut.2012.01.020 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 028BI UT WOS:000310397400001 PM 22858194 ER PT J AU Prudente, S Dallapiccola, B Pellegrini, F Doria, A Trischitta, V AF Prudente, S. Dallapiccola, B. Pellegrini, F. Doria, A. Trischitta, V. TI Genetic prediction of common diseases. Still no help for the clinical diabetologist! SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Review DE Common multifactorial diseases; Genome-wide association studies; Genetic counseling; Direct-to consumer testing; Ethical, legal and social issues; Diseases prediction models; Next generation sequencing ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; HEART-DISEASE; WHOLE-GENOME; RISK-FACTORS; CARDIOVASCULAR-DISEASE; GLUCOSE-METABOLISM; INSULIN-RESISTANCE; PROSPECTIVE COHORT AB Genome-wide association studies (GWAS) have identified several loci associated with many common, multifactorial diseases which have been recently used to market genetic testing directly to the consumers. We here addressed the clinical utility of such GWAS-derived genetic information in predicting type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) in diabetic patients. In addition, the development of new statistical approaches, novel technologies of genome sequencing and ethical, legal and social aspects related to genetic testing have been also addressed. Available data clearly show that, similarly to what reported for most common diseases, genetic testing offered today by commercial companies cannot be used as predicting tools for T2DM and CAD. Further studies taking into account the complex interaction between genes as well as between genetic and non-genetic factors, including age, obesity and glycemic control which seem to modify genetic effects on the risk of T2DM and CAD, might mitigate such negative conclusions. Also, addressing the role of relatively rare variants by next generation sequencing may help identify novel and strong genetic markers with an important role in genetic prediction. Finally, statistical tools concentrated on reclassifying patients might be a useful application of genetic information for predicting many common diseases. By now, prediction of such diseases, including those of interest for the clinical diabetologist, have to be pursued by using traditional clinical markers which perform well and are not costly. (C) 2012 Elsevier B. V. All rights reserved. C1 [Prudente, S.; Trischitta, V.] IRCCS Casa Sollievo Sofferenza, Mendel Lab, San Giovanni Rotondo, Italy. [Dallapiccola, B.] Bambino Gesu Pediat Hosp, IRCCS, Rome, Italy. [Pellegrini, F.] IRCCS Casa Sollievo Sofferenza, Biostat Unit, San Giovanni Rotondo, Italy. [Pellegrini, F.] Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, DCPE, Biostat Unit, I-66030 Santa Maria Imbaro, Italy. [Doria, A.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Doria, A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Doria, A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Trischitta, V.] IRCCS Casa Sollievo Sofferenza, Res Unit Diabet & Endocrine Dis, San Giovanni Rotondo, Italy. [Trischitta, V.] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. RP Trischitta, V (reprint author), CSS Mendel Inst, Viale Regina Margherita 261, I-00198 Rome, Italy. EM vincenzo.trischitta@uniroma1.it RI Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Dallapiccola, Bruno/K-8692-2016 OI Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X; Dallapiccola, Bruno/0000-0002-5031-1013 FU Italian Ministry of Health, Ricerca Corrente; Fondazione Roma, "Sostegno alla ricerca scientifica biomedica"; National Institute of Health, USA [HL073168] FX This study was supported in part by: Italian Ministry of Health, Ricerca Corrente 2011 and 2012 to SP, BD, FP and VT; Fondazione Roma, "Sostegno alla ricerca scientifica biomedica 2008" to VT; National Institute of Health, USA, grant HL073168 to AD. NR 68 TC 10 Z9 10 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD NOV PY 2012 VL 22 IS 11 BP 929 EP 936 DI 10.1016/j.numecd.2012.04.010 PG 8 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 031LD UT WOS:000310640400001 PM 22819342 ER PT J AU Rabinowits, G Haddad, RI AF Rabinowits, Guilherme Haddad, Robert I. TI Overcoming resistance to EGFR inhibitor in head and neck cancer: A review of the literature SO ORAL ONCOLOGY LA English DT Review DE EGFR inhibitor resistance; Head and neck squamous cell carcinoma; ErbB; Aurora kinase; EGFRvIII; PI3K/Akt; MET; VEGF ID EPIDERMAL-GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; RECEPTOR TYROSINE KINASE; MULTICENTER PHASE-II; MESSENGER-RNA; PLUS CETUXIMAB; FAMILY-MEMBERS; ERBB RECEPTORS; LUNG-CANCER; C-MET AB Head and neck squamous cell carcinoma (HNSCC) affects over half a million people worldwide. Despite advances in therapy, only half of the patients are alive in 5 years. Epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of the tumors, and it is correlated with poor response to treatment and worse outcome. Multiple therapies targeting this pathway have been tested. Cetuximab is the only EGFR inhibitor approved in HNSCC, but response rates are low. More recently, significant interest has focus on identifying mechanisms of acquired and de novo EGFR blockage resistance. Here we review some of these mechanisms and describe strategies to overcome that resistance. Published by Elsevier Ltd. C1 [Rabinowits, Guilherme; Haddad, Robert I.] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Rabinowits, G (reprint author), Dana Farber Canc Inst, 450 Brookline Ave SW430, Boston, MA 02215 USA. EM guilherme_rabinowits@dfci.harvard.edu NR 58 TC 30 Z9 31 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 EI 1879-0593 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 2012 VL 48 IS 11 BP 1085 EP 1089 DI 10.1016/j.oraloncology.2012.06.016 PG 5 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 028OX UT WOS:000310433000011 PM 22840785 ER PT J AU Spence, MM Nguyen, LM Hui, RL Chan, J AF Spence, Michele M. Nguyen, Lynda M. Hui, Rita L. Chan, James TI Evaluation of Clinical and Safety Outcomes Associated with Conversion from Brand-Name to Generic Tacrolimus in Transplant Recipients Enrolled in an Integrated Health Care System SO PHARMACOTHERAPY LA English DT Article DE tacrolimus; drugs; generic; drug substitution; therapeutic equivalency ID RENAL-TRANSPLANTATION; IMMUNOSUPPRESSION; MULTICENTER; EXPERIENCE; PROGRAF; DRUGS AB Study Objective To evaluate clinical and safety outcomes among transplant recipients whose tacrolimus was converted from the brand-name formulation to a generic formulation. Design Retrospective analysis. Data Source Clinical databases and electronic records from a large, integrated health care system in California. Patients A total of 234 clinically stable, adult transplant recipients (renal, liver, and heart) whose tacrolimus was converted from the brand-name formulation to a generic formulation between October 1, 2010, and December 31, 2010, according to a physician-approved protocol. Measurements and Main Results For each patient, pre- and postconversion tacrolimus trough concentrations and serum creatinine concentrations were analyzed. Data were also collected on the percentage of patients who required dosage titration, drug cost savings, and rates of reversion to brand-name tacrolimus, biopsy-proved acute allograft rejections, and mortality. No significant differences were noted in mean +/- SD pre- and postconversion tacrolimus trough levels (6.74 +/- 1.61 vs 6.96 +/- 2.31 ng/ml, p=0.137) or serum creatinine concentrations (1.33 +/- 0.48 vs 1.36 +/- 0.82 mg/dl, p=0.302). The mean +/- SD percent change in tacrolimus trough concentration was 5.63 +/- 32.95%. Thirty-six patients (15.4%) required dosage titration. Six patients (2.6%) reverted back to brand-name tacrolimus. No deaths or acute rejections occurred. Use of the generic product saved each patient an average of $45/month in drug acquisition cost and $26/prescription copayment. Conclusion Clinical experience as well as research data show that use of generic tacrolimus results in trough concentrations that are comparable to the brand-name drug. Given the lack of adverse events reported and the cost savings recognized, conversion from brand-name tacrolimus to generic tacrolimus should be encouraged. Since dosage titration may be required, close therapeutic drug monitoring is recommended. C1 [Spence, Michele M.] Kaiser Permanente, Pharm Outcomes Res Grp, Downey, CA 90242 USA. [Nguyen, Lynda M.] San Francisco VA Med Ctr, Dept Pharm, San Francisco, CA USA. [Hui, Rita L.; Chan, James] Kaiser Permanente, Pharm Outcomes Res Grp, Oakland, CA USA. RP Spence, MM (reprint author), Kaiser Permanente, Pharm Outcomes Res Grp, 12254 Bellflower Blvd, Downey, CA 90242 USA. EM michele.m.spence@kp.org NR 20 TC 18 Z9 18 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2012 VL 32 IS 11 BP 981 EP 987 DI 10.1002/phar.1130 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 030EF UT WOS:000310551200007 PM 23074134 ER PT J AU Hoexter, MQ Fadel, G Felicio, AC Calzavara, MB Batista, IR Reis, MA Shih, MC Pitman, RK Andreoli, SB Mello, MF Mari, JJ Bressan, RA AF Hoexter, Marcelo Q. Fadel, Gustavo Felicio, Andre C. Calzavara, Mariana B. Batista, Ilza R. Reis, Marilia A. Shih, Ming C. Pitman, Roger K. Andreoli, Sergio B. Mello, Marcelo F. Mari, Jair J. Bressan, Rodrigo A. TI Higher striatal dopamine transporter density in PTSD: an in vivo SPECT study with [Tc-99m]TRODAT-1 SO PSYCHOPHARMACOLOGY LA English DT Article DE Posttraumatic stress disorder; Depression; Corpus striatum; Dopamine transporter; Single-photon emission computed tomography ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSION; URBAN VIOLENCE; GREATER AVAILABILITY; EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; GENE; ASSOCIATION; SYMPTOMS; BINDING AB Some evidence suggests a hyperdopaminergic state in posttraumatic stress disorder (PTSD). The 9-repetition allele (9R) located in the 3' untranslated region of the dopamine transporter (DAT) gene (SLC6A3) is more frequent among PTSD patients. In vivo molecular imaging studies have shown that healthy 9R carriers have increased striatal DAT binding. However, no prior study evaluated in vivo striatal DAT density in PTSD. The objective of this study was to evaluate in vivo striatal DAT density in PTSD. Twenty-one PTSD subjects and 21 control subjects, who were traumatized but asymptomatic, closely matched comparison subjects evaluated with the Clinician-Administered PTSD Scale underwent a single-photon emission computed tomography scan with [(TC)-T-99m]-TRODAT-1. DAT binding potential (DAT-BP) was calculated using the striatum as the region of the interest and the occipital cortex as a reference region. PTSD patients had greater bilateral striatal DAT-BP (mean +/- SD; left, 1.80 +/- 0.42; right, 1.78 +/- 0.40) than traumatized control subjects (left, 1.62 +/- 0.32; right, 1.61 +/- 0.31; p = 0.039 for the left striatum and p = 0.032 for the right striatum). These results provide the first in vivo evidence for increased DAT density in PTSD. Increases in DAT density may reflect higher dopamine turnover in PTSD, which could contribute to the perpetuation and potentiation of exaggerated fear responses to a given event associated with the traumatic experience. Situations that resemble the traumatic event turn to be interpreted as highly salient (driving attention, arousal, and motivation) in detriment of other daily situations. C1 [Hoexter, Marcelo Q.; Fadel, Gustavo; Felicio, Andre C.; Calzavara, Mariana B.; Batista, Ilza R.; Reis, Marilia A.; Shih, Ming C.; Mari, Jair J.; Bressan, Rodrigo A.] Univ Fed Sao Paulo, LiNC, Dept Psiquiatria, BR-04039032 Sao Paulo, Brazil. [Hoexter, Marcelo Q.; Felicio, Andre C.; Batista, Ilza R.; Reis, Marilia A.; Shih, Ming C.; Bressan, Rodrigo A.] Hosp Israelita Albert Einstein, Inst Cerebro, Inst Ensino & Pesquisa, Sao Paulo, Brazil. [Andreoli, Sergio B.] Univ Fed Sao Paulo, Nucleo Estat & Metodol Aplicadas NEMAP, Dept Psiquiatria, BR-04039032 Sao Paulo, Brazil. [Mello, Marcelo F.] Univ Fed Sao Paulo, Programa Atendimento & Pesquisa Violencia PROVE, Dept Psiquiatria, BR-04039032 Sao Paulo, Brazil. [Hoexter, Marcelo Q.; Pitman, Roger K.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hoexter, MQ (reprint author), Univ Fed Sao Paulo, LiNC, Dept Psiquiatria, Rua Pedro de Toledo 669,3 Andar Fundos, BR-04039032 Sao Paulo, Brazil. EM mqhoexter@gmail.com RI Mari, Jair/A-7309-2008; Bressan, Rodrigo/E-9178-2010; Hoexter, Marcelo/D-7620-2013; CALZAVARA, MARIANA/K-2627-2012 OI Mari, Jair/0000-0002-5403-0112; Bressan, Rodrigo/0000-0002-0868-4449; Hoexter, Marcelo/0000-0002-9302-4380; CALZAVARA, MARIANA/0000-0003-4088-9759 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) [2004/15039-0]; Instituto do Cerebro, Instituto de Ensino e Pesquisa do Hospital Israelita Albert Einstein [148-06]; Astra Zeneca; Bristol; Janssen; Lundbeck; Eli Lilly; Novartis; Roche FX This study received financial support in the form of grants provided by the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) to Dr. Mari (grant: 2004/15039-0) and from Instituto do Cerebro, Instituto de Ensino e Pesquisa do Hospital Israelita Albert Einstein to Dr. Bressan (grant: 148-06). This work was presented at the 65th Annual Meeting of the Society of Biological Psychiatry, May 20-22 in New Orleans, LA, USA.; Drs. Hoexter, Fadel, Felicio, Calzavara, Batista, Reis, Shih, Pitman, Andreoli, Mello, and Mari have declared no conflict of interest. Dr. Bressan has received honoraria and/or consultations fees from Astra Zeneca, Bristol, Janssen, and Lundbeck; has received research funding from Janssen, Eli Lilly, Lundbeck, Novartis, and Roche; and is a shareholder of Biomolecular Technology Ltda. NR 60 TC 18 Z9 18 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2012 VL 224 IS 2 BP 337 EP 345 DI 10.1007/s00213-012-2755-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 026ZK UT WOS:000310321400011 PM 22700036 ER PT J AU Moscariello, A Vliegenthart, R Schoepf, UJ Nance, JW Zwerner, PL Meyer, M Townsend, JC Fernandes, V Steinberg, DH Fink, C Oudkerk, M Bonomo, L O'Brien, TX Henzler, T AF Moscariello, Antonio Vliegenthart, Rozemarijn Schoepf, U. Joseph Nance, John W., Jr. Zwerner, Peter L. Meyer, Mathias Townsend, Jacob C. Fernandes, Valerian Steinberg, Daniel H. Fink, Christian Oudkerk, Matthijs Bonomo, Lorenzo O'Brien, Terrence X. Henzler, Thomas TI Coronary CT Angiography versus Conventional Cardiac Angiography for Therapeutic Decision Making in Patients with High Likelihood of Coronary Artery Disease SO RADIOLOGY LA English DT Article ID COMPUTED TOMOGRAPHIC ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; METAANALYSIS; REVASCULARIZATION; ECHOCARDIOGRAPHY AB Purpose: To assess the efficacy of coronary computed tomographic (CT) angiography for therapeutic decision making in patients with high likelihood of coronary artery disease (CAD)-specifically the ability of coronary CT angiography to help differentiate patients without and patients with a need for revascularization and determine the appropriate revascularization procedure. Materials and Methods: The study protocol was approved by institutional review board, with written informed consent from all patients. The study was conducted in compliance with HIPAA. One hundred eighty-five consecutive symptomatic patients (121 men; mean age, 59.4 years +/- 9.7) with a positive single photon emission computed tomography (SPECT) myocardial perfusion study underwent coronary CT angiography and conventional cardiac angiography (hereafter, cardiac catheterization). The management strategy (conservative treatment vs revascularization) and revascularization procedure (percutaneous coronary intervention [PCI] vs coronary artery bypass graft surgery [CABG]) were prospectively selected on the basis of a combination of coronary CT angiography and SPECT. In addition, the authors calculated the accuracy, sensitivity, specificity, and negative and positive predictive values of coronary CT angiography in the detection of obstructive CAD and the selection of a revascularization strategy. Cardiac catheterization was used as the standard of reference. Results: Of the 185 patients, 113 (61%) did not undergo revascularization and 42 (23%) were free of CAD. In 178 patients (96%), the same therapeutic strategy (conservative treatment vs revascularization) was chosen on the basis of coronary CT angiography and catheterization. All patients in need of revascularization were identified with coronary CT angiography. When revascularization was indicated, the same procedure (PCI vs CABG) was chosen in 66 of 72 patients (92%). Conclusion: In patients with high likelihood of CAD, the performance of coronary CT angiography in the differentiation of patients without and patients with a need for revascularization and the selection of a revascularization strategy was similar to that of cardiac catheterization; accordingly, coronary CT angiography has the potential to limit the number of patients without obstructive CAD who undergo cardiac catheterization and to inform decision making regarding revascularization. C1 [Moscariello, Antonio; Vliegenthart, Rozemarijn; Schoepf, U. Joseph; Nance, John W., Jr.; Zwerner, Peter L.; Meyer, Mathias; Townsend, Jacob C.; Fernandes, Valerian; Steinberg, Daniel H.; O'Brien, Terrence X.; Henzler, Thomas] Med Univ S Carolina, Heart & Vasc Ctr, Charleston, SC 29425 USA. [Moscariello, Antonio; Bonomo, Lorenzo] Univ Cattolica Sacro Cuore, A Gemelli Hosp, Dept Bioimaging & Radiol Sci, I-00168 Rome, Italy. [Vliegenthart, Rozemarijn; Oudkerk, Matthijs] Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Ctr Med Imaging NE Netherlands, NL-9700 AB Groningen, Netherlands. [Meyer, Mathias; Fink, Christian; Henzler, Thomas] Univ Heidelberg, Med Fac Mannheim, Univ Med Ctr Mannheim, Inst Clin Radiol & Nucl Med, D-6900 Heidelberg, Germany. [Fernandes, Valerian; O'Brien, Terrence X.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Schoepf, UJ (reprint author), Med Univ S Carolina, Heart & Vasc Ctr, Ashley River Tower,25 Courtenay Dr, Charleston, SC 29425 USA. EM schoepf@musc.edu RI Meyer, Mathias/G-6791-2015 FU GE Healthcare; Bracco Diagnostics; Siemens Healthcare; Department of Veterans Affairs; Bayer; Bracco; Medrad; Siemens FX Supported in part through research grants provided by GE Healthcare, Bracco Diagnostics, and Siemens Healthcare, as well as through the Research and Development Program of the Department of Veterans Affairs.; A.M. Financial activities related to the present article: institution received a grant from GE Healthcare, Bracco Diagnostics, and Siemens Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. R. V. No relevant conflicts of interest to disclose. U.J.S. Financial activities related to the present article: institution received a grant from GE Healthcare, Bracco Diagnostics, and Siemens Healthcare. Financial activities not related to the present article: is a paid consultant for Bayer, Bracco, GE Healthcare, Medrad, and Siemens; institution received a grant or has a grant pending from Bayer, Bracco, GE Healthcare, Medrad, and Siemens; receives payment for lectures including service on speakers bureaus from Bayer, Bracco, GE Healthcare, Medrad, and Siemens; institution received payment for development of educational presentations from GE Healthcare. Other relationships: none to disclose. J.W.N. No relevant conflicts of interest to disclose. P.L.Z. Financial activities related to the present article: institution received a grant from GE Healthcare, Bracco Diagnostics, and Siemens Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. M. M. Financial activities related to the present article: institution received a grant from GE Healthcare, Bracco Diagnostics, and Siemens Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. J.C.T. Financial activities related to the present article: institution received a grant from GE Healthcare, Bracco Diagnostics, and Siemens Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. V. F. No relevant conflicts of interest to disclose. D. H. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a paid consultant for Boston Scientific, Terumo Interventional Systems, Medtronic, Medicine's Company, Abbott Vascular, and Astra Zeneca. Other relationships: none to disclose. C. F. No relevant conflicts of interest to disclose. M.O. No relevant conflicts of interest to disclose. L. B. No relevant conflicts of interest to disclose. T.X.O. No relevant conflicts of interest to disclose. T. H. No relevant conflicts of interest to disclose. NR 17 TC 17 Z9 18 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2012 VL 265 IS 2 BP 385 EP 392 DI 10.1148/radiol.12112426 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029PN UT WOS:000310508000010 PM 22875799 ER PT J AU Maurovich-Horvat, P Schlett, CL Alkadhi, H Nakano, M Stolzmann, P Vorpahl, M Scheffel, H Tanaka, A Warger, WC Maehara, A Ma, SX Kriegel, MF Kaple, RK Seifarth, H Bamberg, F Mintz, GS Tearney, GJ Virmani, R Hoffmann, U AF Maurovich-Horvat, Pal Schlett, Christopher L. Alkadhi, Hatem Nakano, Masataka Stolzmann, Paul Vorpahl, Marc Scheffel, Hans Tanaka, Atsushi Warger, William C., II Maehara, Akiko Ma, Shixin Kriegel, Matthias F. Kaple, Ryan K. Seifarth, Harald Bamberg, Fabian Mintz, Gary S. Tearney, Guillermo J. Virmani, Renu Hoffmann, Udo TI Differentiation of Early from Advanced Coronary Atherosclerotic Lesions: Systematic Comparison of CT, Intravascular US, and Optical Frequency Domain Imaging with Histopathologic Examination in ex Vivo Human Hearts SO RADIOLOGY LA English DT Article ID MULTISLICE COMPUTED-TOMOGRAPHY; COHERENCE TOMOGRAPHY; PROGNOSTIC VALUE; ARTERY-DISEASE; IN-VIVO; INTRACORONARY ULTRASOUND; VULNERABLE PLAQUE; ROW CT; ANGIOGRAPHY; QUANTIFICATION AB Purpose: To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. Materials and Methods: All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen kappa statistic. Results: Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both P < .0001), while mixed plaque at coronary CT angiography, calcified plaque at intravascular US, and lipid-rich plaque at OFDI were associated with advanced lesions (OR: 2.49, P = .0003; OR: 2.60, P = .002; and OR: 31.2, P < .0001, respectively). OFDI had higher accuracy for discriminating early from advanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, P < .0001). Interobserver agreement was excellent for OFDI and coronary CT angiography (kappa = 0.87 and 0.85, respectively) and was good for intravascular US (kappa = 0.66). Conclusion: Systematic and standardized comparison between invasive and non-invasive modalities for coronary plaque characterization in ex vivo specimens demonstrated that coronary CT angiography and intravascular US are reasonably associated with plaque composition and lesion grading according to histopathologic findings, while OFDI was strongly associated. These data may help to develop initial concepts of sequential imaging strategies to identify patients with advanced coronary plaques. C1 [Maurovich-Horvat, Pal; Schlett, Christopher L.; Alkadhi, Hatem; Stolzmann, Paul; Scheffel, Hans; Kriegel, Matthias F.; Seifarth, Harald; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Kaple, Ryan K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tanaka, Atsushi; Warger, William C., II; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Maurovich-Horvat, Pal] Semmelweis Univ, Ctr Heart, H-1085 Budapest, Hungary. [Nakano, Masataka; Vorpahl, Marc; Virmani, Renu] CV Path Inst, Gaithersburg, MD USA. [Alkadhi, Hatem; Stolzmann, Paul] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Bamberg, Fabian] Univ Munich, Klinikum Grosshadern, Dept Clin Radiol, D-8000 Munich, Germany. [Maehara, Akiko; Ma, Shixin; Mintz, Gary S.] Columbia Univ, Cardiovasc Res Fdn, New York, NY USA. [Seifarth, Harald] Univ Munster, Dept Clin Radiol, D-4400 Munster, Germany. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org OI Maurovich-Horvat, Pal/0000-0003-0885-736X FU GE Healthcare, Milwaukee, Wis; Deutsche Forschungsgemeinschaft (DFG) [Se 2029/1-1]; Volcano; Boston Scientific; Terumo; American Air Liquide; Flatley Discovery Lab; [TAMOP-4.2.1/B-09/1/KMR-2010-0001] FX Supported in part by an unrestricted grant from GE Healthcare, Milwaukee, Wis. P. M. supported by TAMOP-4.2.1/B-09/1/KMR-2010-0001. H. Seifarth supported by a grant from Deutsche Forschungsgemeinschaft (DFG Se 2029/1-1).; P.M. Financial activities related to the present article: institution received grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. C. L. S. Financial activities related to the present article: institution received unrestricted research grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. H. A. No relevant conflicts of interest to disclose. M.N. No relevant conflicts of interest to disclose. P. S. No relevant conflicts of interest to disclose. M. V. No relevant conflicts of interest to disclose. H. Scheffel Financial activities related to the present article: institution received unrestricted research grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. A. T. No relevant conflicts of interest to disclose. W. C. W. No relevant conflicts of interest to disclose. A. M. No relevant conflicts of interest to disclose. S. M. Financial activities related to the present article: institution received unrestricted research grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. M. F. K. Financial activities related to the present article: institution received unrestricted research grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. R. K. K. No relevant conflicts of interest to disclose. H. Seifarth No relevant conflicts of interest to disclose. F. B. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is on the speakers bureau of Siemens Healthcare. Other relationships: none to disclose. G. S. M. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: is a consultant for Volcano; has grants or grants pending with Volcano and Boston Scientific; is on the speakers bureau of Boston Scientific; has received payment for development of educational presentations from Boston Scientific. Other relationships: none to disclose. G.J.T. Financial activities related to the present article: is a consultant for Samsung; institution receives money for nonclinical sponsored research from Terumo. Financial activities not related to the present article: is a consultant for NinePoint Medical; institution has grants or grants pending from American Air Liquide, and Flatley Discovery Lab; is on the speakers bureau of Merck; institution receives royalties from Terumo. Other relationships: none to disclose. R. V. No relevant conflicts of interest to disclose. U. H. Financial activities related to the present article: institution received grant from GE Healthcare. Financial activities not related to the present article: none to disclose. Other relationships: none to disclose. NR 33 TC 15 Z9 16 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2012 VL 265 IS 2 BP 393 EP 401 DI 10.1148/radiol.12111891 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029PN UT WOS:000310508000011 PM 23012461 ER PT J AU Rathmell, JP AF Rathmell, James P. TI American Society of Regional Anesthesia and Pain Medicine 2011 John J. Bonica Award Lecture The Evolution of the Field of Pain Medicine SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article C1 [Rathmell, James P.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pain Med, Boston, MA 02116 USA. [Rathmell, James P.] Harvard Univ, Sch Med, Boston, MA USA. RP Rathmell, JP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Div Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02116 USA. EM rathmell.james@mgh.harvard.edu NR 12 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 2012 VL 37 IS 6 BP 652 EP 656 DI 10.1097/AAP.0b013e3182738c11 PG 5 WC Anesthesiology SC Anesthesiology GA 028OM UT WOS:000310431800017 PM 23086350 ER PT J AU Stone, JH AF Stone, John H. TI IgG4-related disease: nomenclature, clinical features, and treatment SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE IgG4-related disease; Autoimmune pancreatitis; Chronic sclerosing sialadenitis; Retroperitoneal fibrosis; Rituximab ID COMPLICATING AUTOIMMUNE PANCREATITIS; HEPATIC INFLAMMATORY PSEUDOTUMOR; CHRONIC SCLEROSING SIALADENITIS; IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; EOSINOPHILIC ANGIOCENTRIC FIBROSIS; IGG4-POSITIVE PLASMA-CELLS; SYSTEMIC-DISEASE; SERUM IGG4; RETROPERITONEAL FIBROSIS; TUBULOINTERSTITIAL NEPHRITIS AB Concepts about IgG4-related disease (IgG4-RD) are now emerging swiftly. The condition has been identified in virtually every organ system, and its features are often excellent mimickers of malignancies, infections, and other immune-mediated disorders. Recommendations for nomenclature were proposed by the Organizing Committee of the 2011 International IgG4-related disease Symposium, and guidelines for the pathologic diagnosis of this condition have been published by an international group of experts. Experience with treatment regimens is growing. Glucocorticoids and B-cell depletion strategies both appear to be effective and are the subject of ongoing studies. This article reviews the current thought and understanding of this disease with regard to nomenclature, organ system involvement, and approaches to therapy. (C) 2012 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit,Dept Med, Boston, MA 02114 USA. RP Stone, JH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Rheumatol Unit,Dept Med, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM jhstone@partners.org NR 102 TC 53 Z9 57 U1 0 U2 20 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2012 VL 29 IS 4 BP 177 EP 190 DI 10.1053/j.semdp.2012.08.002 PG 14 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 028AY UT WOS:000310396400002 PM 23068296 ER PT J AU Deshpande, V AF Deshpande, Vikram TI The pathology of IgG4-related disease: critical issues and challenges SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE Autoimmune pancreatitis; IgG4-related disease; IgG4; ANCA-related vasculitis; Inflammatory pseudotumor; Inflammatory myofibroblastic tumor; Lymphoma ID PLASMA-CELLS AB IgG4-related disease (IgG4-RD) is a chronic and relapsing disease. The diagnosis of IgG4-RD is based on a combination of features that include clinical, imaging, serologic, histology, and immunohistochemistry. Nonetheless, histopathology has emerged as the gold standard for the diagnosis of IgG4-RD. Guidelines for the pathologic diagnosis of this condition have been published by an international group of experts: a triumvirate of histologic features allows for a confident diagnosis of IgG4-RD to be made in most cases: (1) a dense lymphoplasmacytic infiltrate, (2) storiform-type fibrosis, and (3) obliterative phlebitis. Elevated numbers of IgG4-positive plasma cells are essential for the diagnosis, but this feature is not sufficient in, and of, itself. IgG4-positive plasma cells are also seen in a variety of inflammatory and neoplastic diseases. An elevated IgG4 to IgG ratio, more than 40%, improves the specificity of this stain. A wide range of inflammatory and neoplastic diseases including antineutrophil cytoplasmic antibody (ANCA)-related vasculitis, chronic infections, mesenchymal neoplasms, carcinoma, and lymphoma should be excluded before arriving at a diagnosis of IgG4-RD. This review aims to provide the histopathologist with a set of practical guidelines for the diagnosis of IgG4-RD, and also addresses the many controversies associated with the diagnostic aspects of this disease. (C) 2012 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 11 TC 30 Z9 32 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2012 VL 29 IS 4 BP 191 EP 196 DI 10.1053/j.semdp.2012.08.001 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 028AY UT WOS:000310396400003 PM 23068297 ER PT J AU Shinagare, S Shinagare, AB Deshpande, V AF Shinagare, Shweta Shinagare, Atul B. Deshpande, Vikram TI Autoimmune pancreatitis: a guide for the histopathologist SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE Autoimmune pancreatitis; IgG4-related disease; IgG4 ID IGG4-RELATED DISEASE; SCLEROSING PANCREATITIS; DIAGNOSTIC-CRITERIA; INFILTRATION; FEATURES AB Autoimmune pancreatitis (AIP) is a distinct form of pancreatitis with a characteristic histological appearance. Clinically and radiologically, many of these patients show enlargement of pancreas and pancreatic duct/bile duct strictures, thus mimicking pancreatic carcinoma. There are 2 forms of the disease: (1) type 1 AIP characterized by storiform type fibrosis, obliterative phlebitis, and elevated numbers of immunoglobulin G4 (IgG4) positive plasma cells, typically >50 per high-power field, and, (2) type 2 AIP characterized by granulocytic epithelial lesions and only occasional IgG4-bearing plasma cells, typically <10 per high-power field. The type I variant of AIP is the pancreatic manifestation of IgG4-related disease, thus both pancreatic and extrapancreatic recurrences are common. The type 2 variant is unrelated to IgG4-related disease, and disease recurrence is uncommon. Both forms of the disease show a swift response to immunosuppressive therapy. This review highlights the clinical and guidelines that assist in pathological differences between the 2 forms of AIP. We also review distinguishing AIP from its closest mimic, pancreatic adenocarcinoma. (C) 2012 Elsevier Inc. All rights reserved. C1 [Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Shinagare, Shweta] Tufts Med Ctr, Dept Pathol, Boston, MA USA. [Shinagare, Atul B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 28 TC 5 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2012 VL 29 IS 4 BP 197 EP 204 DI 10.1053/j.semdp.2012.07.007 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 028AY UT WOS:000310396400004 PM 23068298 ER PT J AU Ferry, JA Deshpande, V AF Ferry, Judith A. Deshpande, Vikram TI IgG4-related disease in the head and neck SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE IgG4-related disease; Orbital pseudolymphoma; Orbital pseudotumor; Dacryoadenitis; Sialadenitis ID CHRONIC SCLEROSING SIALADENITIS; SYSTEMIC-DISEASE; KUTTNER TUMOR; LYMPHOMA; DACRYOADENITIS; GLAND AB Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. With improvements in diagnostic techniques and with advances in lymphoma subclassification, it became clear that many of the dense lymphoid infiltrates, including cases classified as lymphoma and likely some classified as atypical lymphoid hyperplasia, represented low-grade B-cell lymphomas, the most common of which by far were extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas. Ocular adnexal inflammatory pseudotumor, reactive lymphoid hyperplasia, and chronic sclerosing sialadenitis were recognized, but the focus in diagnosis had been on avoiding misdiagnosis as a neoplastic process and in planning appropriate therapy. Recently, it has become clear that many cases of these reactive processes fall into the spectrum of immunoglobulin G4 (IgG4)-related disease, offering new insight into the pathogenesis of inflammatory lesions occurring in the ocular adnexa and the salivary glands. The majority of entities previously classified as chronic sclerosing sialadenitis, Mikulicz disease, orbital pseudolymphoma, and eosinophilic angiocentric fibrosis are now considered a part of the IgG4-related disease spectrum. In this review, we discuss the histologic and immunohistochemical features of IgG4-related disease of the head and neck and provide guidance for distinguishing this disease from its many mimics. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ferry, Judith A.] Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Ferry, Judith A.; Deshpande, Vikram] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. EM jferry@partners.org NR 31 TC 26 Z9 29 U1 0 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2012 VL 29 IS 4 BP 235 EP 244 DI 10.1053/j.semdp.2012.07.008 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 028AY UT WOS:000310396400009 PM 23068303 ER PT J AU Wong, H Budha, NR West, K Blackwood, E Ware, JA Yu, R Darbonne, WC Gould, SE Steigerwalt, R Erickson, R Hop, CEAC LoRusso, P Eckhardt, SG Wagner, A Chan, IT Mamounas, M Flygare, JA Fairbrother, WJ AF Wong, Harvey Budha, Nageshwar R. West, Kristina Blackwood, Elizabeth Ware, Joseph A. Yu, Ron Darbonne, Walter C. Gould, Stephen E. Steigerwalt, Ronald Erickson, Rebecca Hop, Cornelis E. A. C. LoRusso, Patricia Eckhardt, S. Gail Wagner, Andrew Chan, Iris T. Mamounas, Michael Flygare, John A. Fairbrother, Wayne J. TI Dogs Are More Sensitive to Antagonists of Inhibitor of Apoptosis Proteins Than Rats and Humans: A Translational Toxicokinetic/Toxicodynamic Analysis SO TOXICOLOGICAL SCIENCES LA English DT Article DE TK; TD; PK; PD; pharmacokinetic-pharmacodynamic; toxicodynamics; toxicokinetics; IAP ID ALPHA-DEPENDENT APOPTOSIS; IAP ANTAGONISTS; THERAPEUTIC TARGETS; INDUCE; AUTOUBIQUITINATION; ENDOTOXIN; CANCER; CIAP1 AB Inhibitor of apoptosis (IAP) proteins suppress apoptosis and are overexpressed in a variety of cancers. GDC-0152 is a potent and selective IAP antagonist being developed as an anticancer agent. In preclinical safety studies, dogs were particularly sensitive to GDC-0152 showing adverse signs of a tumor necrosis factor alpha (TNF-) driven systemic inflammatory response, related to cellular IAP degradation and activation of NFB signaling, at lower exposures compared with rat. In addition, downstream increases in systemic levels of cytokines and chemokines, such as monocyte chemotactic protein-1 (MCP-1), were observed. A semimechanistic population toxicokinetic/toxicodynamic (TK/TD) model incorporating transit compartments was used to fit MCP-1 plasma concentrations from rats or dogs given iv GDC-0152 doses. Estimated TD parameters inferred that lower GDC-0152 plasma concentrations triggered more severe increases in plasma MCP-1 in dogs compared with rats. Human simulations performed using dog TD parameters and human pharmacokinetics predicted 3002400% increases of MCP-1 in humans at iv doses from 0.76 to 1.48mg/kg. Similar simulations using rat TD parameters suggest little or no change. Patients given iv doses of GDC-0152 up to 1.48mg/kg iv showed no substantial increases in systemic MCP-1 or signs of a severe TNF- driven systemic inflammatory response. Emerging clinical data reported for other IAP antagonists are consistent with our observations. Taken together, the data suggest dogs are more sensitive to IAP antagonists compared with humans and rats. This study illustrates how TK/TD analysis can be utilized to quantitatively translate and context an identified preclinical safety risk in dogs to humans. C1 [Wong, Harvey; Hop, Cornelis E. A. C.] Genentech Inc, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA. [Budha, Nageshwar R.; Ware, Joseph A.] Genentech Inc, Dept Clin Pharmacol, San Francisco, CA 94080 USA. [West, Kristina; Blackwood, Elizabeth; Gould, Stephen E.] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA. [Yu, Ron] Genentech Inc, Dept Biostat, San Francisco, CA 94080 USA. [Darbonne, Walter C.] Genentech Inc, Dept PD Biomarkers, San Francisco, CA 94080 USA. [Steigerwalt, Ronald; Erickson, Rebecca] Genentech Inc, Dept Safety Assessment, San Francisco, CA 94080 USA. [LoRusso, Patricia] Karmanos Canc Inst, Detroit, MI USA. [Eckhardt, S. Gail] Univ Colorado, Ctr Canc, Denver, CO 80262 USA. [Wagner, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, Iris T.] Genentech Inc, Oncol Exploratory Clin Dev, San Francisco, CA 94080 USA. [Mamounas, Michael] Genentech Inc, Portfolio Management & Operat, San Francisco, CA 94080 USA. [Flygare, John A.] Genentech Inc, Med Chem, San Francisco, CA 94080 USA. [Fairbrother, Wayne J.] Genentech Inc, Early Stage Discovery Biochem, San Francisco, CA 94080 USA. RP Wong, H (reprint author), Genentech Inc, Dept Drug Metab & Pharmacokinet, 1 DNA Way,MS 412A, San Francisco, CA 94080 USA. EM wong.harvey@gene.com FU Genentech FX This research was funded by entirely by Genentech. NR 28 TC 10 Z9 10 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2012 VL 130 IS 1 BP 205 EP 213 DI 10.1093/toxsci/kfs235 PG 9 WC Toxicology SC Toxicology GA 025CV UT WOS:000310163200018 PM 22843607 ER PT J AU Machtinger, EL Wilson, TC Haberer, JE Weiss, DS AF Machtinger, E. L. Wilson, T. C. Haberer, J. E. Weiss, D. S. TI Psychological Trauma and PTSD in HIV-Positive Women: A Meta-Analysis SO AIDS AND BEHAVIOR LA English DT Review DE HIV/AIDS; Women; Trauma; PTSD; Meta-analysis ID POSTTRAUMATIC-STRESS-DISORDER; NATIONAL COMORBIDITY SURVEY; CHILDHOOD SEXUAL-ABUSE; HUMAN-IMMUNODEFICIENCY-VIRUS; INTIMATE PARTNER VIOLENCE; HEALTH-CARE-UTILIZATION; DSM-IV DISORDERS; LOW-INCOME WOMEN; QUALITY-OF-LIFE; INFECTED WOMEN AB Women bear an increasing burden of the HIV epidemic and face high rates of morbidity and mortality. Trauma has been increasingly associated with the high prevalence and poor outcomes of HIV in this population. This meta-analysis estimates rates of psychological trauma and posttraumatic stress disorder (PTSD) in HIV-positive women from the United States. We reviewed 9,552 articles, of which 29 met our inclusion criteria, resulting in a sample of 5,930 individuals. The findings demonstrate highly disproportionate rates of trauma exposure and recent PTSD in HIV-positive women compared to the general population of women. For example, the estimated rate of recent PTSD among HIV-positive women is 30.0% (95% CI 18.8-42.7%), which is over five-times the rate of recent PTSD reported in a national sample of women. The estimated rate of intimate partner violence is 55.3% (95% CI 36.1-73.8%), which is more than twice the national rate. Studies of trauma-prevention and trauma-recovery interventions in this population are greatly needed. C1 [Machtinger, E. L.; Wilson, T. C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Haberer, J. E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Haberer, J. E.] Ctr Global Hlth, Boston, MA USA. [Weiss, D. S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Machtinger, EL (reprint author), Univ Calif San Francisco, Dept Med, 400 Parnassus Ave,Box 0320, San Francisco, CA 94143 USA. EM edward.machtinger@ucsf.edu FU NIMH NIH HHS [K24 MH087227] NR 71 TC 65 Z9 65 U1 5 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2012 VL 16 IS 8 BP 2091 EP 2100 DI 10.1007/s10461-011-0127-4 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 026XK UT WOS:000310316200001 PM 22249954 ER PT J AU Machtinger, EL Haberer, JE Wilson, TC Weiss, DS AF Machtinger, E. L. Haberer, J. E. Wilson, T. C. Weiss, D. S. TI Recent Trauma is Associated with Antiretroviral Failure and HIV Transmission Risk Behavior Among HIV-Positive Women and Female-Identified Transgenders SO AIDS AND BEHAVIOR LA English DT Article DE Women living with HIV/AIDS; Trauma; PTSD; Antiretroviral failure; Prevention with positives ID POSTTRAUMATIC-STRESS-DISORDER; CHILDHOOD SEXUAL-ABUSE; MEDICATION ADHERENCE; UNITED-STATES; INFECTED WOMEN; GENDER-DIFFERENCES; DOMESTIC VIOLENCE; PARTNER VIOLENCE; SOCIAL SUPPORT; MENTAL-HEALTH AB Trauma and posttraumatic stress disorder disproportionally affect HIV-positive women. Studies increasingly demonstrate that both conditions may predict poor HIV-related health outcomes and transmission-risk behaviors. This study analyzed data from a prevention-with-positives program to understand if socio-economic, behavioral, and health-related factors are associated with antiretroviral failure and HIV transmission-risk behaviors among 113 HIV-positive biological and transgender women. An affirmative answer to a simple screening question for recent trauma was significantly associated with both outcomes. Compared to participants without recent trauma, participants reporting recent trauma had over four-times the odds of antiretroviral failure (AOR 4.3; 95% CI 1.1-16.6; p = 0.04), and over three-times the odds of reporting sex with an HIV-negative or unknown serostatus partner (AOR 3.9; 95% CI 1.3-11.9; p = 0.02) and < 100% condom use with these partners (AOR 4.5; 95% CI 1.5-13.3; p = 0.007). Screening for recent trauma in HIV-positive biological and transgender women identifies patients at high risk for poor health outcomes and HIV transmission-risk behavior. C1 [Machtinger, E. L.; Wilson, T. C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Haberer, J. E.] Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, Boston, MA 02114 USA. [Weiss, D. S.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. RP Machtinger, EL (reprint author), Univ Calif San Francisco, Dept Med, 400 Parnassus Ave,Box 0320, San Francisco, CA 94143 USA. EM Edward.Machtinger@ucsf.edu NR 70 TC 26 Z9 26 U1 3 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2012 VL 16 IS 8 BP 2160 EP 2170 DI 10.1007/s10461-012-0158-5 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 026XK UT WOS:000310316200005 PM 22426597 ER PT J AU Ramirez-Avila, L Regan, S Giddy, J Chetty, S Ross, D Katz, JN Freedberg, KA Walensky, RP Losina, E Bassett, IV AF Ramirez-Avila, Lynn Regan, Susan Giddy, Janet Chetty, Senica Ross, Douglas Katz, Jeffrey N. Freedberg, Kenneth A. Walensky, Rochelle P. Losina, Elena Bassett, Ingrid V. TI Depressive Symptoms and Their Impact on Health-seeking Behaviors in Newly-diagnosed HIV-infected Patients in Durban, South Africa SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Linkage to care; Depressive symptoms; Depression; South Africa; Africa ID QUALITY-OF-LIFE; ACTIVE ANTIRETROVIRAL THERAPY; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; HIV/AIDS PATIENTS; MAJOR DEPRESSION; INDIVIDUALS; PREVALENCE; PREDICTORS; INITIATION AB We evaluated the prevalence and correlates of depressive symptoms prior to HIV diagnosis and determined the effect of these symptoms on seeking HIV care at an urban and rural clinic in Durban, South Africa. Adults were administered a questionnaire which included the 5-item Mental Health Index (MHI-5) before HIV testing. We determined the depressive symptoms among HIV-infected subjects. Of 1,545 newly-diagnosed HIV-infected subjects, 55% had depressive symptoms by MHI-5 score. Enrolling at the urban clinic and decreasing functional activity score were associated with depressive symptoms. Subjects with depressive symptoms who were referred for HIV testing by a healthcare provider were less likely to obtain a CD4 count than those without depressive symptoms who self-referred for testing. Depressive symptoms were common among newly-diagnosed HIV-infected participants and impacted CD4 uptake. Depression screening at the time of HIV diagnosis is critical for improving linkage to mental health and HIV services in South Africa. C1 [Ramirez-Avila, Lynn] Childrens Hosp, Div Infect Dis, Boston, MA 02139 USA. [Ramirez-Avila, Lynn; Regan, Susan; Freedberg, Kenneth A.; Walensky, Rochelle P.; Losina, Elena; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Ramirez-Avila, Lynn; Regan, Susan; Freedberg, Kenneth A.; Walensky, Rochelle P.; Losina, Elena; Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Giddy, Janet; Chetty, Senica] McCord Hosp, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Durban, South Africa. [Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Katz, Jeffrey N.; Losina, Elena] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.; Losina, Elena; Bassett, Ingrid V.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Dept Biostat, Boston, MA 02215 USA. RP Ramirez-Avila, L (reprint author), Childrens Hosp, Div Infect Dis, 333 Longwood Ave, Boston, MA 02139 USA. EM lynn.ramirez@childrens.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X; Regan, Susan/0000-0003-0940-2017 FU NIAID NIH HHS [K23 AI068458, T32 AI 007433, P30 AI042851, P30 AI42851, P30 AI060354, R01 AI058736, K24 AI062476, T32 AI007433]; NICHD NIH HHS [T32 HD055148, T32 HD 055148-02]; NIMH NIH HHS [R01MH090326, R01 MH090326, R01 MH073445] NR 35 TC 11 Z9 11 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2012 VL 16 IS 8 BP 2226 EP 2235 DI 10.1007/s10461-012-0160-y PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 026XK UT WOS:000310316200012 PM 22451351 ER PT J AU Blashill, AJ O'Cleirigh, C Mayer, KH Goshe, BM Safren, SA AF Blashill, Aaron J. O'Cleirigh, Conall Mayer, Kenneth H. Goshe, Brett M. Safren, Steven A. TI Body Mass Index, Depression and Sexual Transmission Risk Behaviors Among HIV-Positive MSM SO AIDS AND BEHAVIOR LA English DT Article DE HIV/AIDS; BMI; Depression; MSM; Sexual transmission risk ID UNITED-STATES; MEN; OBESITY; CARE; PREVALENCE; SYMPTOMS; IMAGE; SATISFACTION; ASSOCIATION; POPULATION AB Depression has been shown to be a risk factor for serodiscordant unprotected anal intercourse (SDUAI) in some studies, but not others. Body mass index (BMI) has recently been associated with SDUAI; however, to date, no published study has investigated the interactive effect of depression and BMI on SDUAI. The current study assessed the association between depression, BMI, and SDUAI among HIV-positive MSM. Participants were 430 HIV-positive MSM recruited in a Boston community health center where they received primary care. Participants completed audio computer-assisted self interview (ACASI) measures. Objective height and weight and other clinical variables were accessed through participants' electronic medical records. Depression was positively associated with SDUAI. This association was significantly moderated by BMI. Elevated levels of depression were only associated with SDUAI for underweight participants. These findings suggest that underweight, depressed HIV-positive MSM may be particularly likely to engage in SDUAI. C1 [Blashill, Aaron J.; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Blashill, Aaron J.; O'Cleirigh, Conall; Mayer, Kenneth H.; Goshe, Brett M.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mayer, Kenneth H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02114 USA. RP Blashill, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org FU NIMH NIH HHS [5R01MH068746-05, K24 MH094214, R01 MH068746]; PHS HHS [H97HA01293] NR 33 TC 10 Z9 10 U1 4 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD NOV PY 2012 VL 16 IS 8 BP 2251 EP 2256 DI 10.1007/s10461-011-0056-2 PG 6 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 026XK UT WOS:000310316200015 PM 21983696 ER PT J AU Goncalves, PD Cunha, PJ Malbergier, A do Amaral, RA de Oliveira, LG Yang, JJ de Andrade, AG AF Goncalves, Priscila Dib Cunha, Paulo Jannuzzi Malbergier, Andre do Amaral, Ricardo Abrantes de Oliveira, Lucio Garcia Yang, Jasmine J. de Andrade, Arthur Guerra TI The association between low alcohol use and traffic risk behaviors among Brazilian college students SO ALCOHOL LA English DT Article DE College drinking; Automobile driving; Risk behaviors ID DRUG-USE; PREFRONTAL CORTEX; DRIVING BEHAVIOR; DRINKING; CONSEQUENCES; CONSUMPTION; PREVALENCE; CRASHES; DRIVER; BRAIN AB Although there are a large number of studies focused on binge drinking and traffic risk behaviors (TRB), little is known regarding low levels of alcohol consumption and its association to TRB. The aim of this cross-sectional study is to examine the association of low to moderate alcohol intake pattern and TRB in college students in Brazil. 7037 students from a National representative sample were selected under rigorous inclusion criteria. All study participants voluntarily fulfilled a structured, anonymous, and self-questionnaire regarding alcohol and drug use, social-demographic data, and TRB. Alcohol was assessed according to the average number of alcoholic units consumed on standard occasions over the past 12 months. The associations between alcohol intake and TRB were summarized with odds ratio and their confidence interval obtained from logistic regression. Compared with abstainers students who consumed only one alcohol unit had the risk of being a passenger in a car driven by a drunk driver increased by almost four times, students who reported using five or more units were increased by almost five times the risk of being involved in a car crash. Compared with students who consumed one alcohol unit, the risk of driving under the influence of alcohol increased four times in students using three alcohol units. Age group, use of illicit drugs, employment status, gender, and marital status significantly influenced occurrence of TRB among college students. Our study highlights the potential detrimental effects of low and moderate pattern of alcohol consumption and its relation to riding with an intoxicated driver and other TRB. These data suggest that targeted interventions should be implemented in order to prevent negative consequences due to alcohol use in this population. (C) 2012 Elsevier Inc. All rights reserved, C1 [Goncalves, Priscila Dib; Cunha, Paulo Jannuzzi; Malbergier, Andre; do Amaral, Ricardo Abrantes; de Oliveira, Lucio Garcia; de Andrade, Arthur Guerra] Univ Sao Paulo, Interdisciplinary Grp Studies Alcohol & Drugs GRE, Inst Psychiat IPq, Sch Med, BR-05403010 Sao Paulo, Brazil. [Goncalves, Priscila Dib] Univ Sao Paulo, Psychol & Neuropsychol Serv, Inst Psychiat IPq, Sch Med, BR-05403010 Sao Paulo, Brazil. [Goncalves, Priscila Dib; Cunha, Paulo Jannuzzi] Univ Sao Paulo, Lab Psychiat Neuroimaging LIM 21, Dept Psychiat, Sch Med, BR-05403010 Sao Paulo, Brazil. [Cunha, Paulo Jannuzzi] Univ Sao Paulo, Equilibrium Program, Dept Psychiat, Sch Medicine, BR-01135000 Sao Paulo, Brazil. [Yang, Jasmine J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Goncalves, PD (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, GREA, Rua Ovidio Pires de Campos 785, BR-05403010 Sao Paulo, Brazil. EM pri_dib@yahoo.com.br RI Andrade, Arthur/O-1964-2015 NR 53 TC 7 Z9 7 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV PY 2012 VL 46 IS 7 BP 673 EP 679 DI 10.1016/j.alcohol.2012.08.002 PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 020GE UT WOS:000309796200008 PM 22921955 ER PT J AU Kaiser, NC Melrose, RJ Liu, C Sultzer, DL Jimenez, E Su, M Monserratt, L Mendez, MF AF Kaiser, Natalie C. Melrose, Rebecca J. Liu, Collin Sultzer, David L. Jimenez, Elvira Su, Michael Monserratt, Lorena Mendez, Mario F. TI Neuropsychological and Neuroimaging Markers in Early Versus Late-Onset Alzheimer's Disease SO AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS LA English DT Article DE early onset; late onset; neuropsychology; Alzheimer's disease; dementia; neuroimaging; FDG-PET ID ISCHEMIC VASCULAR DEMENTIA; MENTAL-STATE-EXAMINATION; GLUCOSE-METABOLISM; EXECUTIVE DEFICITS; SENILE DEMENTIA; AGE; PERFORMANCE; POPULATION; PATTERNS; DISTURBANCES AB Background: Early-onset Alzheimer's disease (EOAD) has been overshadowed by the more common late-onset AD (LOAD). Yet, the literature indicates EOAD may have less hippocampal-memory presentations and more focal neocortical localization early in the disease. Objective: To evaluate these proposed differences between these 2 forms of AD and to explore what they inform about differences in AD pathophysiology. Methods: In all, 21 patients with EOAD and 24 patients with LOAD matched for disease progression and severity were compared on neurocognitive measures and resting state fluorodeoxy-glucose positron-emission tomography (FDG-PET). Results: Patients with EOAD had worse executive functions with greater hypometabolism in the parietal regions; whereas patients with LOAD had worse confrontation naming and verbal recognition memory with greater hypometabolism in inferior frontotemporal regions. Conclusions: In addition to highlighting significant differences between EOAD and LOAD, these results reveal dissociation between executive deficits in AD and frontal hypometabolism, suggesting early disturbances of the parietal-frontal network in EOAD. C1 [Kaiser, Natalie C.; Liu, Collin; Sultzer, David L.; Jimenez, Elvira; Monserratt, Lorena; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Melrose, Rebecca J.; Sultzer, David L.; Su, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Kaiser, NC (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 401,Room A235, Los Angeles, CA 90073 USA. EM natalie.kaiser@va.gov FU NIH [R01AG034499-3]; Department of Veterans Affairs VA Merit Review; Career Development Award; NIMH [R01-MH56031] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: NIH Grant #R01AG034499-3 (M. Mendez PI); Department of Veterans Affairs VA Merit Review (2 separate awards; 1 to M. Mendez and another to D. Sultzer); Career Development Award to R. Melrose; NIMH #R01-MH56031 (D. Sultzer,) PI. NR 47 TC 11 Z9 11 U1 3 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1533-3175 J9 AM J ALZHEIMERS DIS JI Am. J. Alzheimers Dis. Other Dement. PD NOV PY 2012 VL 27 IS 7 BP 520 EP 529 DI 10.1177/1533317512459798 PG 10 WC Geriatrics & Gerontology; Clinical Neurology SC Geriatrics & Gerontology; Neurosciences & Neurology GA 022AX UT WOS:000309928500010 PM 22990206 ER PT J AU Fritsma, GA Dembitzer, FR Randhawa, A Marques, M Van Cott, EM Adcock, D Peerschke, EI AF Fritsma, George A. Dembitzer, Francine R. Randhawa, Ankush Marques, Marisa Van Cott, Elizabeth M. Adcock, Dorothy Peerschke, Ellinor I. TI APTT Reagents for Different Coagulation Tests: One Size Does Not Fit All Reply SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 [Fritsma, George A.] Your Interact Hemostasis Resource, Fritsma Factor, Trussville, AL USA. [Dembitzer, Francine R.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Randhawa, Ankush] Precis BioLog, Dartmouth, NS, Canada. [Marques, Marisa] Univ Alabama Birmingham, Birmingham, AL USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Adcock, Dorothy] Esoterix Coagulat, Englewood, CO USA. [Peerschke, Ellinor I.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Peerschke, Ellinor I.] Weill Cornell Med Coll, New York, NY USA. RP Fritsma, GA (reprint author), Your Interact Hemostasis Resource, Fritsma Factor, Trussville, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 2012 VL 138 IS 5 BP 757 EP 758 PG 2 WC Pathology SC Pathology GA 024PH UT WOS:000310120600019 ER PT J AU Hodgson, MJ Mohr, DC Drummond, DJ Bell, M Van Male, L AF Hodgson, Michael J. Mohr, David C. Drummond, David J. Bell, Margaret Van Male, Lynn TI Managing disruptive patients in health care: Necessary solutions to a difficult problem SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE accident prevention; veterans; professional staff committees; safety management; employee occupational health ID WORKPLACE VIOLENCE; ASSAULTS; SURVEILLANCE; PREVENTION; SETTINGS; NURSES; SYSTEM AB Background We sought to describe the components and processes in a violence risk assessment and management system, including electronic record requirements in the Veterans Health Administration (VA). We present information on system-level variation among program elements and their association with perceived and measured effectiveness. Methods We conducted a cross-sectional survey of Chiefs of Staff (COS) at 140 VA hospitals across the United States about specific disruptive behavior program elements, such as committee processes, patient referrals, and outcome patterns. We assessed COS perceived effectiveness of the processes. We compared COS perceptions with employee-reported assault-related incident rates and workers compensation lost time claim rates for assault-related injuries for 2009 and 2010. Results We found the violence risk assessment and management system is heavily used, often with guidance to provide police protection for providers. COS respondents were generally satisfied with design and performance of the system. Committee processes and perceptions of effectiveness were associated with reduction in assault-related incident rates. Conclusions VA's system was considered effective by system owners and users may be effective at reducing assaulted-related injuries. Am. J. Ind. Med. 55:10091017, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Van Male, Lynn] Vet Hlth Adm, Off Publ Hlth, Behav Threat Management Program, Washington, DC USA. [Mohr, David C.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Dept Vet Affairs, Boston, MA USA. [Mohr, David C.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Drummond, David J.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. [Bell, Margaret] Vet Hlth Adm, Patient Care Serv, Milwaukee, WI USA. RP Mohr, DC (reprint author), VA Boston Healthcare Syst 152M, Ctr Org Leadership & Management Res, 150 S Huntington Ave, Boston, MA 02130 USA. EM david.mohr2@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development FX Contract grant sponsor: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research and Development. NR 33 TC 3 Z9 4 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD NOV PY 2012 VL 55 IS 11 BP 1009 EP 1017 DI 10.1002/ajim.22104 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 023VX UT WOS:000310066200006 PM 22911609 ER PT J AU Khor, TS Badizadegan, K Ferrone, C Fernandez-del Castillo, C Desai, GS Saenz, A Le, L Lauwers, GY Deshpande, V AF Khor, Tze S. Badizadegan, Kamran Ferrone, Cristina Fernandez-del Castillo, Carlos Desai, Gaurav S. Saenz, Adam Le, Long Lauwers, Gregory Y. Deshpande, Vikram TI Acinar Cystadenoma of the Pancreas A Clinicopathologic Study of 10 Cases Including Multilocular Lesions With Mural Nodules SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE acinar cell cystadenoma; acinar cell cystadenocarcinoma; pancreatic cystic neoplasms; histogenesis; differential diagnosis ID CELL CYSTADENOMA; CYSTIC TRANSFORMATION; IN-VITRO; DIFFERENTIATION; TRANSDIFFERENTIATION; PLASTICITY; CARCINOMA; NEOPLASMS; LESIONS; ENTITY AB Pancreatic acinar cystadenomas (ACAs) are rare cystic lesions showing acinar differentiation with benign outcome. Although debated, ACAs are favored to be neoplastic and potentially the benign counterpart of acinar cystadenocarcinoma. We present the largest single institution series to date comprising 10 cases. The mean age was 49 years with a female predominance (M:F = 1:2.3). Abdominal/flank pain was the most common presentation (n = 6). Serum amylase/lipase and cyst fluid amylase were often elevated. All lesions had a benign outcome on follow-up (5 to 67 mo). The lesions were unilocular (n = 3) or multilocular (n = 7) with mean size of 3.8 cm (range, 2.9 to 5.0 cm) and 5.1 cm (range, 2.0 to 7.5 cm), respectively. Eight lesions were unifocal with locations as follows: head (n = 2), head/neck (n = 2), body (n = 1), tail (n = 1), predominantly extrapancreatic with a microscopic intrapancreatic component (n = 1), and unspecified location (n = 1). Two lesions were multifocal, involving the head/uncinate/body and pancreatic head, respectively. Two aspects of ACAs that may represent a diagnostic pitfall include the propensity for acinar epithelium to appear as nondescript flat/cuboidal epithelium (trypsin/chymotrypsin immunopositive) and epithelial heterogeneity, with focal mucinous and squamous epithelium, the latter particularly in multilocular variants. In addition, 2 cases with intracystic nodules were observed. Array comparative genomic hybridization performed on 1 of these cases showed multiple chromosomal gains involving 1p, 3p, 5q, 6p, 7q, 8, 10q, 11, 14, 20, and X. These findings provide preliminary evidence that ACAs represent a cystic neoplastic lesion. C1 [Khor, Tze S.; Badizadegan, Kamran; Le, Long; Lauwers, Gregory Y.; Deshpande, Vikram] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02478 USA. [Ferrone, Cristina; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02478 USA. [Desai, Gaurav S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02478 USA. [Ferrone, Cristina; Fernandez-del Castillo, Carlos; Lauwers, Gregory Y.; Deshpande, Vikram] Harvard Univ, Sch Med, Boston, MA USA. [Saenz, Adam] Madigan Army Med Ctr, Ft Lewis, WA USA. [Khor, Tze S.] PathWest Lab Med, Dept Anat Pathol, Perth, WA, Australia. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02478 USA. EM vdeshpande@partners.org NR 33 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2012 VL 36 IS 11 BP 1579 EP 1591 DI 10.1097/PAS.0b013e318265fa4b PG 13 WC Pathology; Surgery SC Pathology; Surgery GA 023TW UT WOS:000310059600001 PM 23060352 ER PT J AU Fujita, H Lennerz, JKM Chung, DC Patel, D Deshpande, V Yoon, SS Lauwers, GY AF Fujita, Hiroshi Lennerz, Jochen K. M. Chung, Daniel C. Patel, Devanshi Deshpande, Vikram Yoon, Sam S. Lauwers, Gregory Y. TI Endoscopic Surveillance of Patients With Hereditary Diffuse Gastric Cancer Biopsy Recommendations After Topographic Distribution of Cancer Foci in a Series of 10 CDH1-mutated Gastrectomies SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastric cancer; hereditary; CDH1; familial; surveillance ID FAMILIAL ADENOMATOUS POLYPOSIS; CADHERIN MUTATION CARRIERS; CLINICAL MANAGEMENT; GERMLINE MUTATIONS; TOTAL GASTRECTOMY; RISK; CDH1; INDIVIDUALS; GUIDELINES; EXPERIENCE AB The management of hereditary diffuse-type gastric cancer revolves around surveillance biopsies and the timing of prophylactic gastrectomy. In the absence of a validated surveillance biopsy protocol, we modeled bioptic diagnostic yield on the basis of the topographic distribution of cancer foci in a series of 10 gastrectomies in CDH1-mutation carriers. Complete histologic examination was performed in all cases, and 1817 slides were evaluated for the presence of in situ, intramucosal, or submucosal diffuse-type carcinoma. Detailed maps determined the density of cancer foci. On the basis of the number of sampled glands per biopsy in routine surveillance preoperative endoscopy, we estimated the theoretical number of biopsies necessary for a 90% rate of detection of neoplastic foci, and we evaluated this number, taking into account the regional distribution of these foci. A total of 96m of gastric mucosa with similar to 1,193,453 gastric glands yielded 302 cancer foci [in situ (n = 89), intramucosal (n = 209), and submucosal (n = 4)] spanning the width of a total of 1820 glands (8 to 1205 per case; average 182 +/- 115). On the basis of the number of glands per stomach and the average number of glands sampled during surveillance biopsy (28.7 +/- 1.7; range, 0 to 79; n = 112), the theoretical number of biopsies necessary to capture at least 1 cancer focus was estimated to be 1768 (range, 50 to 5832) to assure a 90% detection rate. Mapping of cancer foci showed the highest density in the anterior proximal fundus (37%) and cardia/proximal fundus (27%). Our results argue for the incorporation of cancer focus distribution into any biopsy protocol, although detection is likely to remain extremely low, and they call into question the validity of endoscopic surveillance. C1 [Fujita, Hiroshi; Lennerz, Jochen K. M.; Deshpande, Vikram; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chung, Daniel C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Yoon, Sam S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Chung, Daniel C.; Patel, Devanshi] Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Fujita, Hiroshi] Kagoshima Univ, Dept Digest & Life Style Related Dis, Grad Sch Med & Dent Sci, Kagoshima 890, Japan. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,WRN 219, Boston, MA 02114 USA. EM glauwers@partners.org NR 28 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2012 VL 36 IS 11 BP 1709 EP 1717 DI 10.1097/PAS.0b013e31826ca204 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 023TW UT WOS:000310059600014 PM 23073328 ER PT J AU VanderVeen, JW Gulliver, SB Morissette, SB Kruse, MI Kamholz, BW Zimering, RT Knight, J Keane, TM AF VanderVeen, Joseph W. Gulliver, Suzy B. Morissette, Sandra B. Kruse, Marc I. Kamholz, Barbara W. Zimering, Rose T. Knight, Jeffrey Keane, Terence M. TI Differences in Drinking Patterns, Occupational Stress, and Exposure to Potentially Traumatic Events among Firefighters: Predictors of Smoking Relapse SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; UNITED-STATES; ALCOHOL-USE; RELIABILITY; CESSATION; TOBACCO; ADULTS AB Background and Objectives: Despite the increased awareness regarding the risks of cigarette smoking, this behavior continues to be a serious public health concern. As such, the goal of the current study was to examine risk factors for smoking relapse among individuals employed through fire service. Methods: In this report, drinking changes, trauma exposure, and occupational stress were compared among firefighters (N = 81) who reported a relapse to cigarette smoking (n = 27), a lifetime former history of smoking (n = 27), or no history of smoking (n = 27). Mechanisms behind tobacco relapse occurring after employment in fire service were explored. Results: Firefighters who relapsed to smoking, when compared to their nonsmoking peers, had higher rates of weekly alcohol consumption throughout their first year of fire service and had greater increases in drinking from preacademy to postacademy. Conclusions and Scientific Significance: Gaining a better understanding of these behaviors within this understudied and high-risk population may provide valuable information that can be used in designing future relapse prevention strategies as well as smoking cessation interventions. (Am J Addict 2012;21:550554) C1 [VanderVeen, Joseph W.; Gulliver, Suzy B.; Morissette, Sandra B.; Kruse, Marc I.] VISN 17 Ctr Excellence Res Returning War Vet, Waco, TX USA. [VanderVeen, Joseph W.; Gulliver, Suzy B.; Morissette, Sandra B.; Kruse, Marc I.] Texas A&M Hlth Sci Ctr, Dept Psychiat & Behav Sci, Temple, TX USA. [Kamholz, Barbara W.; Zimering, Rose T.; Knight, Jeffrey; Keane, Terence M.] VA Boston Healthcare Syst, Boston, MA USA. [Kamholz, Barbara W.; Zimering, Rose T.; Knight, Jeffrey; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Zimering, Rose T.; Knight, Jeffrey; Keane, Terence M.] Natl Ctr PTSD, Boston, MA USA. RP VanderVeen, JW (reprint author), GV Sonny Montgomery VAMC, 1500 E Woodrow Wilson, Jackson, MS 39216 USA. EM Joseph.VanderVeen2@va.gov FU NIMH NIH HHS [R01 MH073808] NR 28 TC 2 Z9 2 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD NOV-DEC PY 2012 VL 21 IS 6 BP 550 EP 554 DI 10.1111/j.1521-0391.2012.00282.x PG 5 WC Substance Abuse SC Substance Abuse GA 027ED UT WOS:000310333700008 PM 23082834 ER PT J AU Lajoie, TM Rich, A AF Lajoie, Travis M. Rich, Anne TI "Bath Salts": A New Drug Epidemic-A Case Report SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article C1 [Lajoie, Travis M.] Oregon Hlth & Sci Univ, Dept Psychiat, Portland VA Med Ctr, Portland, OR 97201 USA. [Rich, Anne] Univ Utah, Sch Med, Dept Psychiat, Salt Lake City, UT 84112 USA. RP Lajoie, TM (reprint author), 1052 Emerson Ave, Salt Lake City, UT 84105 USA. EM tmlajoie@hotmail.com NR 6 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD NOV-DEC PY 2012 VL 21 IS 6 BP 572 EP 573 DI 10.1111/j.1521-0391.2012.00286.x PG 2 WC Substance Abuse SC Substance Abuse GA 027ED UT WOS:000310333700013 PM 23082840 ER PT J AU Wood, JB Smith, DB Baker, EH Brecher, SM Gupta, K AF Wood, Jameson B. Smith, Donald B. Baker, Errol H. Brecher, Stephen M. Gupta, Kalpana TI Has the Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus Increased Trimethoprim-Sulfamethoxazole Use and Resistance?: a 10-Year Time Series Analysis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ACUTE UNCOMPLICATED CYSTITIS; CLINICAL-PRACTICE GUIDELINES; URINARY-TRACT-INFECTIONS; SOFT-TISSUE INFECTIONS; ANTIMICROBIAL RESISTANCE; ESCHERICHIA-COLI; SULFONAMIDE RESISTANCE; ANTIBIOTIC USE; GENOME SIZE; PREVALENCE AB There are an increasing number of indications for trimethoprim-sulfamethoxazole use, including skin and soft tissue infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Assessing the relationship between rates of use and antibiotic resistance is important for maintaining the expected efficacy of this drug for guideline-recommended conditions. Using interrupted time series analysis, we aimed to determine whether the 2005 emergence of CA-MRSA and recommendations of trimethoprim-sulfamethoxazole as the preferred therapy were associated with changes in trimethoprim-sulfamethoxazole use and susceptibility rates. The data from all VA Boston Health Care System facilities, including 118,863 inpatient admissions, 6,272,661 outpatient clinic visits, and 10,138 isolates were collected over a 10-year period. There was a significant (P = 0.02) increase in trimethoprim-sulfamethoxazole prescriptions in the post-CA-MRSA period (1,605/year) compared to the pre-CA-MRSA period (1,538/year). Although the overall susceptibility of Escherichia coli and Proteus spp. to trimethoprim-sulfamethoxazole decreased over the study period, the rate of change in the pre- versus the post-CA-MRSA period was not significantly different. The changes in susceptibility rates of S. aureus to trimethoprim-sulfamethoxazole and to methicillin were also not significantly different. The CA-MRSA period is associated with a significant increase in use of trimethoprim-sulfamethoxazole but not with significant changes in the rates of susceptibilities among clinical isolates. There is also no evidence for selection of organisms with increased resistance to other antimicrobials in relation to increased trimethoprim-sulfamethoxazole use. C1 [Baker, Errol H.; Brecher, Stephen M.; Gupta, Kalpana] VA Boston Hlth Care Syst, Dept Med, Boston, MA USA. [Wood, Jameson B.; Smith, Donald B.] VA Boston Hlth Care Syst, Dept Pharm, Boston, MA USA. [Baker, Errol H.; Brecher, Stephen M.; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Gupta, K (reprint author), VA Boston Hlth Care Syst, Dept Med, Boston, MA USA. EM kalpana.gupta@va.gov NR 35 TC 10 Z9 11 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2012 VL 56 IS 11 BP 5655 EP 5660 DI 10.1128/AAC.01011-12 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 023SN UT WOS:000310055800028 PM 22908161 ER PT J AU Ripplinger, CM Kessinger, CW Li, CQ Kim, JW McCarthy, JR Weissleder, R Henke, PK Lin, CP Jaffer, FA AF Ripplinger, Crystal M. Kessinger, Chase W. Li, Chunqiang Kim, Jin Won McCarthy, Jason R. Weissleder, Ralph Henke, Peter K. Lin, Charles P. Jaffer, Farouc A. TI Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo Assessment by Multimodal Fluorescence Molecular Imaging SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE deep vein thrombosis; inflammation; macrophage; molecular imaging; post-thrombotic syndrome ID DEEP-VEIN THROMBOSIS; POSTTHROMBOTIC SYNDROME; MOUSE MODEL; CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; PLASMINOGEN; RECRUITMENT; MICROSCOPY; LEUKOCYTES; RAT AB Objective-Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2 integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results-Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy. Day 4 analyses showed robust relationships among in vivo thrombus macrophages, matrix metalloproteinase activity, and fluorescein isothiocyanate-dextran deposition (r>0.70; P<0.01). In a serial 2-time point study, mice with DVT underwent intravital microscopy at day 4 and day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (P<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography was used and detected macrophages within jugular DVT (P<0.05 versus sham controls). Conclusion-Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo and can inform the magnitude of thrombus resolution. (Arterioscler Thromb Vasc Biol. 2012;32:2616-2624.) C1 [Ripplinger, Crystal M.; Kessinger, Chase W.; Kim, Jin Won; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Cardiovasc Res Ctr, Boston, MA 02114 USA. [Li, Chunqiang; Lin, Charles P.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [McCarthy, Jason R.; Weissleder, Ralph; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. [McCarthy, Jason R.; Weissleder, Ralph; Lin, Charles P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Ripplinger, Crystal M.] Univ Calif Davis, Sch Med, Dept Pharmacol, Davis, CA 95616 USA. [Kim, Jin Won] Korea Univ, Guro Hosp, Ctr Cardiovasc, Seoul, South Korea. [Henke, Peter K.] Univ Michigan, Dept Surg, Vasc Surg Sect, Ann Arbor, MI 48109 USA. RP Jaffer, FA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Cardiovasc Res Ctr, 185 Cambridge St,Suite 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU American Heart Association [0830352N]; Howard Hughes Medical Institute; National Institutes of Health (NIH) [R01 HL 108229-01A1, T32 HL07208, U24CA092782] FX This work was supported by American Heart Association Scientist Development grant number 0830352N (to F.A.J.), Howard Hughes Medical Institute Career Development Award (to F.A.J.), National Institutes of Health (NIH) R01 HL 108229-01A1 (to F.A.J.), NIH T32 HL07208 (to C. M. R.), and NIH U24CA092782 Small Animal Imaging Resource (to R.W.). NR 37 TC 11 Z9 13 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2012 VL 32 IS 11 BP 2616 EP + DI 10.1161/ATVBAHA.112.251983 PG 20 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 023TP UT WOS:000310058900014 PM 22995524 ER PT J AU Tang, WHW Hartiala, J Fan, YY Wu, YP Stewart, AFR Erdmann, J Kathiresan, S Roberts, R McPherson, R Allayee, H Hazen, SL AF Tang, W. H. Wilson Hartiala, Jaana Fan, Yiying Wu, Yuping Stewart, Alexandre F. R. Erdmann, Jeanette Kathiresan, Sekar Roberts, Robert McPherson, Ruth Allayee, Hooman Hazen, Stanley L. CA CARDIoGRAM Consortium TI Clinical and Genetic Association of Serum Paraoxonase and Arylesterase Activities With Cardiovascular Risk SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE paraoxonase 1 gene; coronary artery disease; oxidative stress; arylesterase activity ID CORONARY-ARTERY-DISEASE; ATHEROSCLEROSIS; PON1; MICE; POLYMORPHISM AB Objective-Diminished serum paraoxonase and arylesterase activities (measures of paraoxonase-1 [PON-1] function) in humans have been linked to heightened systemic oxidative stress and atherosclerosis risk. The clinical prognostic use of measuring distinct PON-1 activities has not been established, and the genetic determinants of PON-1 activities are not known. Methods and Results-We established analytically robust high-throughput assays for serum paraoxonase and arylesterase activities and measured these in 3668 stable subjects undergoing elective coronary angiography without acute coronary syndrome and were prospectively followed for major adverse cardiovascular events (MACE=death, myocardial infarction, stroke) over 3 years. Low serum arylesterase and paraoxonase activities were both associated with increased risk for MACE, with arylesterase activity showing greatest prognostic value (quartile 4 versus quartile 1; hazard ratio 2.63; 95% CI, 1.97-3.50; P < 0.01). Arylesterase remained significant after adjusting for traditional risk factors, C-reactive protein, and creatinine clearance (hazard ratio, 2.20; 95% CI, 1.60-3.02; P < 0.01), predicted future development of MACE in both primary and secondary prevention populations, and reclassified risk categories incrementally to traditional clinical variables. A genome-wide association study identified distinct single nucleotide polymorphisms within the PON-1 gene that were highly significantly associated with serum paraoxonase (1.18x10(-303)) or arylesterase (4.99x10(-116)) activity but these variants were not associated with either 3-year MACE risk in an angiographic cohort (n=2136) or history of either coronary artery disease or myocardial infarction in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis consortium (n approximate to 80 000 subjects). Conclusion-Diminished serum arylesterase activity, but not the genetic determinants of PON-1 functional measures, provides incremental prognostic value and clinical reclassification of stable subjects at risk of developing MACE. (Arterioscler Thromb Vasc Biol. 2012;32:2803-2812.) C1 [Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Dept Cell Biol, Ctr Cardiovasc Diagnost & Prevent, Lerner Res Inst, Cleveland, OH 44106 USA. [Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Dept Cardiovasc Med, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. [Fan, Yiying; Wu, Yuping] Cleveland State Univ, Dept Math, Cleveland, OH 44115 USA. [Stewart, Alexandre F. R.; Roberts, Robert; McPherson, Ruth] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON, Canada. [Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23538 Lubeck, Germany. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Hazen, SL (reprint author), 9500 Euclid Ave,NE-10, Cleveland, OH 44195 USA. EM hazens@ccf.org RI Tang, Wai Hong/I-1238-2013; Erdmann, Jeanette/P-7513-2014 OI Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231 FU National Institutes of Health [P01HL076491-055328, 5P01HL103453, P01HL098055, R01HL103866, 1P20HL113452, 1R01HL103931, R01ES021801]; Fondation Leducq; Cleveland Clinic Clinical Research Unit of the Case Western Reserve University Clinical and Translational Sciences Award [UL1TR 000439-06]; Leonard Krieger Fund; Canadian Institutes of Health Research (CIHR); Medical Research Council Operating Grant Program [(MOP)-82810]; Canada Foundation for Innovation (CFI) [11966]; Heart and Stroke Foundation of Ontario (HSFO) [NA6001]; CIHR [MOP172605, MOP77682]; Abbott Laboratories, Inc. FX This research was supported by National Institutes of Health grants P01HL076491-055328, 5P01HL103453, and the Fondation Leducq. The GeneBank study has been supported by National Institutes of Health grants P01HL098055, R01HL103866, 1P20HL113452, 1R01HL103931, R01ES021801 (Dr Allayee), and the Cleveland Clinic Clinical Research Unit of the Case Western Reserve University Clinical and Translational Sciences Award (UL1TR 000439-06). Dr Hazen is also partially supported by a gift from the Leonard Krieger Fund. The John and Jennifer Ruddy Canadian Cardiovascular Genetics Centre investigators are supported by Canadian Institutes of Health Research (CIHR) #Medical Research Council Operating Grant Program (MOP)-82810, Canada Foundation for Innovation (CFI) #11966, Heart and Stroke Foundation of Ontario (HSFO) #NA6001, CIHR #MOP172605, and CIHR #MOP77682.; Dr Tang has received research grant support from Abbott Laboratories, Inc. Dr Hazen reports being listed as coinventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics. Dr Hazen reports having been paid as a consultant or speaker for the following companies: Abbott Diagnostics, Cleveland Heart Lab, Esperion, Lilly, Liposcience Inc, Merck & Co, Inc, and Pfizer Inc. Dr Hazen reports receiving research funds from Abbott, Cleveland Heart Lab, Liposcience Inc, and Pfizer Inc. Dr Hazen reports having the right to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from the companies shown below: Abbott Laboratories, Inc, Cleveland Heart Lab, Esperion, Frantz Biomarkers, LLC, Liposcience Inc, and Siemens. The other authors have no conflicts to report. There are no medical writers or editors involved in the preparation of the manuscript. NR 16 TC 55 Z9 56 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 2012 VL 32 IS 11 BP 2803 EP + DI 10.1161/ATVBAHA.112.253930 PG 25 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 023TP UT WOS:000310058900036 PM 22982463 ER PT J AU Sulik, KK O'Leary-Moore, SK Charness, ME Riley, EP AF Sulik, K. K. O'Leary-Moore, S. K. Charness, M. E. Riley, E. P. TI 'Better safe than sorry'- better for whom? SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Letter C1 [Sulik, K. K.; O'Leary-Moore, S. K.] Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27515 USA. [Sulik, K. K.] Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC USA. [O'Leary-Moore, S. K.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Charness, M. E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Charness, M. E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Riley, E. P.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. RP Sulik, KK (reprint author), Univ N Carolina, Dept Cell & Dev Biol, Chapel Hill, NC 27515 USA. RI Riley, Edward/E-6369-2013 OI Riley, Edward/0000-0001-8747-891X NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD NOV PY 2012 VL 119 IS 12 BP 1547 EP 1547 DI 10.1111/j.1471-0528.2012.03497.x PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 019OP UT WOS:000309749500020 ER PT J AU O'Neil-Pirozzi, TM Goldstein, R Strangman, GE Glenn, MB AF O'Neil-Pirozzi, Therese M. Goldstein, Richard Strangman, Gary E. Glenn, Mel B. TI Test-re-test reliability of the Hopkins Verbal Learning Test-Revised in individuals with traumatic brain injury SO BRAIN INJURY LA English DT Article DE Test-re-test reliability; traumatic brain injury; memory ID TEST-RETEST RELIABILITY; RELIABLE CHANGE INDEXES; VIRTUAL PLANNING TEST; CLOSED HEAD-INJURY; ALTERNATE FORMS; MEMORY TESTS; REHABILITATION; RECOGNITION; RIVASTIGMINE; DEVICES AB Primary objective: To determine test-re-test reliability of the Hopkins Verbal Learning Test-Revised (HVLT-R) in a group of individuals with traumatic brain injury (TBI). Research design: Single-group repeated measures design. Methods and procedures: Seventy-five individuals with TBI were administered the HVLT-R twice, with 6-8 weeks between the two test sessions. Main outcomes and results: Test-re-test reliability on HVLT-R scoring parameters ranged from 0.537-0.818, with seven of the eight scoring parameters exhibiting r>0.6. At re-test, scores did not significantly change on any of the eight HVLT-R scoring parameters. Conclusions: HVLT-R use with individuals with TBI is supported. Test-re-test reliability of total recall and delayed recall sub-scores was particularly high. C1 [O'Neil-Pirozzi, Therese M.] Northeastern Univ, Speech Language Pathol & Audiol Dept, Boston, MA 02115 USA. [O'Neil-Pirozzi, Therese M.; Goldstein, Richard; Strangman, Gary E.; Glenn, Mel B.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Goldstein, Richard; Glenn, Mel B.] Harvard Univ, Sch Med, Boston, MA USA. [Strangman, Gary E.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP O'Neil-Pirozzi, TM (reprint author), Northeastern Univ, Speech Language Pathol & Audiol Dept, 103 Forsyth Bldg, Boston, MA 02115 USA. EM t.oneil-pirozzi@neu.edu FU National Institute on Disability and Rehabilitation Research, US Department of Education [H133A020513] FX This work was supported in part by grant #H133A020513 from the National Institute on Disability and Rehabilitation Research, US Department of Education. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. NR 44 TC 7 Z9 7 U1 1 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD NOV PY 2012 VL 26 IS 12 BP 1425 EP 1430 DI 10.3109/02699052.2012.694561 PG 6 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 022DL UT WOS:000309935400003 PM 22715921 ER PT J AU Arvold, ND Oh, KS Niemierko, A Taghian, AG Lin, NU Abi-Raad, RF Sreedhara, M Harris, JR Alexander, BM AF Arvold, Nils D. Oh, Kevin S. Niemierko, Andrzej Taghian, Alphonse G. Lin, Nancy U. Abi-Raad, Rita F. Sreedhara, Meera Harris, Jay R. Alexander, Brian M. TI Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 28-31, 2012 CL Boston, MA SP Amer Soc Radiat Oncol (ASTRO) DE Brain metastases; Breast cancer; Subtype; Breast-conserving therapy ID CANCER SUBTYPES; SURVIVAL; RECURRENCE; RADIOTHERAPY; INVOLVEMENT; PROGNOSIS AB The characteristics of brain metastases (BM) that develop after breast-conserving therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We examined 1,434 consecutive patients with stage I/II invasive BC who received BCT from 1997 to 2006, 91 % of whom received adjuvant systemic therapy, according to BC subtype. Median follow-up was 85 months. Overall 5-year cumulative incidence of BM was 1.7 %; 0.1 % for luminal A, 3.3 % for luminal B, 3.2 % for luminal-HER2, 3.7 % for HER2, and 7.4 % for triple negative (TN). Women who developed BM were more likely at BC diagnosis to be younger (P < .0001) and have node-positive (P < .0001), grade 3 (P < .0001), hormone receptor-negative (P = .006), and HER2-positive (P = .01) tumors. Median time from BC diagnosis to BM was 51.4 months (range, 7.6-108 months), which was longer among luminal versus non-luminal subtypes (P = .0002; median, 61.4 vs. 34.5 months). Thirty-four percent of patients who developed distant metastases (DM) eventually developed BM. Median time from DM to BM was 12.8 months but varied by subtype, including 7.4 months for TN, 9.6 months for luminal B, and 27.1 months for HER2. Eighty-one percent of all BM patients presented with neurologic symptoms. Median number of BM at diagnosis was two, and median BM size was 15 mm, with TN (27 mm) and luminal B (16 mm) exhibiting the largest median sizes. In conclusion, the risk of BM after BCT varies significantly by subtype. Given the large size and symptomatic presentation among luminal B and TN subtypes, earlier BM detection might improve quality of life or increase eligibility for non-invasive treatments including stereotactic radiosurgery. Women with DM from these two BC subtypes have a high incidence of BM with a short latency, suggesting an ideal target population for trials evaluating the utility of MRI screening. C1 [Arvold, Nils D.; Sreedhara, Meera; Harris, Jay R.; Alexander, Brian M.] Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Oh, Kevin S.; Niemierko, Andrzej; Taghian, Alphonse G.; Abi-Raad, Rita F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Lin, Nancy U.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA. RP Arvold, ND (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM narvold@partners.org NR 21 TC 21 Z9 21 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2012 VL 136 IS 1 BP 153 EP 160 DI 10.1007/s10549-012-2243-x PG 8 WC Oncology SC Oncology GA 022FF UT WOS:000309940300014 PM 22968656 ER PT J AU Mayer, EL Isakoff, SJ Klement, G Downing, SR Chen, WY Hannagan, K Gelman, R Winer, EP Burstein, HJ AF Mayer, Erica L. Isakoff, Steven J. Klement, Giannoula Downing, Sean R. Chen, Wendy Y. Hannagan, Keri Gelman, Rebecca Winer, Eric P. Burstein, Harold J. TI Combination antiangiogenic therapy in advanced breast cancer: a phase 1 trial of vandetanib, a VEGFR inhibitor, and metronomic chemotherapy, with correlative platelet proteomics SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Angiogenesis inhibition; Breast cancer; Metronomic chemotherapy; Proteomics; Vandetanib ID ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; 1ST-LINE TREATMENT; ANTITUMOR-ACTIVITY; PLUS DOCETAXEL; DOUBLE-BLIND; ANGIOGENESIS; BEVACIZUMAB; TUMOR AB This phase 1 study evaluated the safety and tolerability of antiangiogenic therapy using vandetanib and metronomic cyclophosphamide and methotrexate in metastatic breast cancer. Eligible patients had metastatic breast cancer with 0-4 prior chemotherapy regimens. All received cyclophosphamide 50 mg daily, methotrexate 2.5 mg days 1-2 weekly, and vandetanib daily in 3 dose-escalation cohorts: 100 mg (C1), 200 mg (C2), and 300 mg (C3). The primary endpoint was safety and tolerability; secondary endpoints included response rate and evaluation of platelet-associated proteins. Twenty three patients were treated and evaluable for toxicity. Common mild toxicities included nausea, vomiting, LFTs abnormalities, fatigue, and rash. Three episodes of dose-limiting toxicity occurred in C3. In all cohorts, 1/3 of patients required vandetanib dose reduction, and 22 % ended therapy for toxicity. Of the 20 response-evaluable patients, 10 % demonstrated partial response and 15 % stable disease a parts per thousand yen24 weeks. Proteomic analyses demonstrated changes in platelet content of angiogenesis regulators, including vascular endothelial growth factor and platelet factor 4, with exposure to therapy. This regimen was tolerable at a maximum vandetanib dose of 200 mg; modest clinical activity was observed in this heavily pretreated population. Changes in the platelet proteome may serve as pharmacodynamic markers of angiogenesis inhibition. Metronomic chemotherapy is an attractive partner with biologics and deserves further study in metastatic breast cancer. C1 [Mayer, Erica L.; Chen, Wendy Y.; Hannagan, Keri; Gelman, Rebecca; Winer, Eric P.; Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. [Mayer, Erica L.; Chen, Wendy Y.; Winer, Eric P.; Burstein, Harold J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. [Isakoff, Steven J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02215 USA. [Klement, Giannoula] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Downing, Sean R.] Fdn Med, Cambridge, MA USA. RP Mayer, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM emayer@partners.org FU Investigator-Sponsored Study Program of AstraZeneca, Wilmington, DE FX This research was supported by a grant from the Investigator-Sponsored Study Program of AstraZeneca, Wilmington, DE NR 53 TC 11 Z9 11 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2012 VL 136 IS 1 BP 169 EP 178 DI 10.1007/s10549-012-2256-5 PG 10 WC Oncology SC Oncology GA 022FF UT WOS:000309940300016 PM 23001754 ER PT J AU Shaikh, AY Maan, A Heist, EK Tighe, DA Aurigemma, GP McManus, DD AF Shaikh, Amir Y. Maan, Abhishek Heist, E. Kevin Tighe, Dennis A. Aurigemma, Gerard P. McManus, David D. TI Management Strategies in Atrial Fibrillation in Patients With Heart Failure SO CARDIOLOGY IN REVIEW LA English DT Review DE atrial fibrillation; heart failure; rate control; rhythm control; catheter ablation; antiarrhythmic drugs ID LEFT-VENTRICULAR DYSFUNCTION; CARDIAC-RESYNCHRONIZATION THERAPY; CONVERTING-ENZYME-INHIBITORS; RANDOMIZED CONTROLLED-TRIALS; PRESERVED EJECTION FRACTION; ANTIARRHYTHMIC-DRUG THERAPY; PLACEBO-CONTROLLED TRIAL; PULMONARY-VEIN ISOLATION; SINUS RHYTHM; CATHETER ABLATION AB Atrial fibrillation (AF) and heart failure (HF) frequently occur together, and their coexistence is associated with a poor prognosis. AF and HF share risk factors, but their relationship involves complex hemodynamic, neurohormonal, inflammatory, ultrastructural, and electrophysiologic processes that extend beyond epidemiological associations. The shared mechanisms underlying AF and HF have important implications for the treatment of AF in patients with HF. This article focuses on reviewing contemporary data as it pertains to AF management in patients with HF and provides insight into investigational therapies currently under development. C1 [McManus, David D.] Univ Massachusetts, Med Ctr, Dept Med, Div Cardiol,Electrophysiol Sect,Med Sch, Worcester, MA 01655 USA. [Heist, E. Kevin] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Heist, E. Kevin] Harvard Univ, Sch Med, Boston, MA USA. RP McManus, DD (reprint author), Univ Massachusetts, Med Ctr, Dept Med, Div Cardiol,Electrophysiol Sect,Med Sch, 55 Lake Ave N, Worcester, MA 01655 USA. EM mcmanusd@ummhc.org NR 120 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1061-5377 J9 CARDIOL REV JI Cardiol. Rev. PD NOV-DEC PY 2012 VL 20 IS 6 BP 288 EP 296 DI 10.1097/CRD.0b013e31825dcf9b PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 020OO UT WOS:000309822300005 PM 22581123 ER PT J AU Sabuncu, MR Buckner, RL Smoller, JW Lee, PH Fischl, B Sperling, RA AF Sabuncu, Mert R. Buckner, Randy L. Smoller, Jordan W. Lee, Phil Hyoun Fischl, Bruce Sperling, Reisa A. CA Alzheimer's Dis Neuroimaging TI The Association between a Polygenic Alzheimer Score and Cortical Thickness in Clinically Normal Subjects SO CEREBRAL CORTEX LA English DT Article DE Alzheimer's disease; imaging genetics; polygenic score ID GENOME-WIDE ASSOCIATION; BRAIN ATROPHY RATES; MILD COGNITIVE IMPAIRMENT; APOE EPSILON-4 ALLELE; HUMAN CEREBRAL-CORTEX; APOLIPOPROTEIN-E; HIPPOCAMPAL ATROPHY; GENETIC RISK; NONDEMENTED INDIVIDUALS; GEOMETRICALLY ACCURATE AB Late-onset Alzheimer's disease (AD) is 50-70% heritable with complex genetic underpinnings. In addition to Apoliprotein E (APOE) epsilon 4, the major genetic risk factor, recent genome-wide association studies (GWAS) have identified a growing list of sequence variations associated with the disease. Building on a prior large-scale AD GWAS, we used a recently developed analytic method to compute a polygenic score that involves up to 26 independent common sequence variants and is associated with AD dementia, above and beyond APOE. We then examined the associations between the polygenic score and the magnetic resonance imaging-derived thickness measurements across AD-vulnerable cortex in clinically normal (CN) human subjects (N = 104). AD-specific cortical thickness was correlated with the polygenic risk score, even after controlling for APOE genotype and cerebrospinal fluid (CSF) levels of beta-amyloid (A beta(1-42)). Furthermore, the association remained significant in CN subjects with levels of CSF A beta(1-42) in the normal range and in APOE epsilon 3 homozygotes. The observation that genetic risk variants are associated with thickness across AD-vulnerable regions of interest in CN older individuals, suggests that the combination of polygenic risk profile, neuroimaging, and CSF biomarkers may hold synergistic potential to aid in the prediction of future cognitive decline. C1 [Sabuncu, Mert R.; Buckner, Randy L.; Fischl, Bruce; Sperling, Reisa A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Sabuncu, Mert R.; Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02128 USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02128 USA. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA 02128 USA. [Smoller, Jordan W.; Lee, Phil Hyoun] Massachusetts Gen Hosp, Richard B Simches Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA. [Sperling, Reisa A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Sperling, Reisa A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sabuncu, MR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM msabuncu@csail.mit.edu FU ADNI; National Institutes of Health (NIH) [U01 AG024904, P01AG036694, P50AG005134, P41RR14074, R01AG021910, R01AG027435, NIBIB 1K25EB013649-01]; National Institute on Aging (NIA) [AG022381]; National Institute of Biomedical Imaging and Bioengineering; National Center for Research Resources [P41-RR14075]; NCRR BIRN Morphometric Project [BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758]; National Center for Alternative Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019, 1S10RR023043]; Autism & Dyslexia Project; Ellison Medical Foundation; Harvard Catalyst, The Harvard Clinical, and Translational Science Center (NIH) [1KL2RR025757-01]; Harvard University; NIH Blueprint for Neuroscience Research [U01-MH093765] FX Data collection and sharing for this project was funded by the ADNI and the National Institutes of Health (NIH) (grant U01 AG024904). The ADNI is funded by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott Laboratories, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation Plc, Genentech Inc, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson Services Inc, Eli Lilly and Company, Medpace Inc, Merck and Co Inc, Novartis International AG, Pfizer Inc, F. Hoffman-La Roche Ltd, Schering-Plough Corporation, CCBR-SYNARC Inc, and Wyeth Pharmaceuticals, as well as nonprofit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the US Food and Drug Administration. Private sector contributions to the ADNI are facilitated by the Foundation for the NIH. The grantee organization is the Northern California Institute for Research and Education Inc, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. The ADNI data are disseminated by the Laboratory for NeuroImaging at the University of California, Los Angeles. This work was supported by NIH grants P01AG036694; P50AG005134; P41RR14074; R01AG021910; and R01AG027435. Further support was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the NIA (AG022381), the National Center for Alternative Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01), and the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. Dr. Sabuncu received support from a KL2 Medical Research Investigator Training (MeRIT) grant awarded via Harvard Catalyst, The Harvard Clinical, and Translational Science Center (NIH grant #1KL2RR025757-01 and financial contributions from Harvard University and its affiliated academic health care centers), and an NIH K25 grant (NIBIB 1K25EB013649-01). Additional support was provided by the NIH Blueprint for Neuroscience Research (U01-MH093765, part of the multi-institutional Human Connectome Project). NR 84 TC 31 Z9 31 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2012 VL 22 IS 11 BP 2653 EP 2661 DI 10.1093/cercor/bhr348 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 018XH UT WOS:000309700700018 PM 22169231 ER PT J AU Gard, T Holzel, BK Sack, AT Hempel, H Lazar, SW Vaitl, D Ott, U AF Gard, Tim Hoelzel, Britta K. Sack, Alexander T. Hempel, Hannes Lazar, Sara W. Vaitl, Dieter Ott, Ulrich TI Pain Attenuation through Mindfulness is Associated with Decreased Cognitive Control and Increased Sensory Processing in the Brain SO CEREBRAL CORTEX LA English DT Article DE lateral prefrontal cortex; meditation; pain modulation; posterior insula; rostral anterior cingulate cortex ID ANTERIOR CINGULATE CORTEX; PLACEBO ANALGESIA; PREFRONTAL CORTEX; FOCUSED ATTENTION; NEURAL RESPONSES; TERM MEDITATION; ZEN MEDITATORS; FMRI; MECHANISMS; EXPERIENCE AB Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms. C1 [Gard, Tim; Hoelzel, Britta K.; Lazar, Sara W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. [Gard, Tim; Hoelzel, Britta K.; Hempel, Hannes; Vaitl, Dieter; Ott, Ulrich] Univ Giessen, Bender Inst Neuroimaging, D-35394 Giessen, Germany. [Sack, Alexander T.] Maastricht Univ, Fac Psychol & Neurosci, Dept Cognit Neurosci, NL-6200 MD Maastricht, Netherlands. [Vaitl, Dieter; Ott, Ulrich] Inst Frontier Areas Psychol & Mental Hlth, D-79098 Freiburg, Germany. RP Gard, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 120 2nd Ave, Charlestown, MA 02129 USA. EM tgard@nmr.mgh.harvard.edu RI Lazar, Sara/G-3809-2012 OI Lazar, Sara/0000-0003-1126-8363 FU German Academic Exchange Service (DAAD); Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme; Dutch Organization for Scientific Research (NWO) [452-06-003] FX T.G. was supported by the German Academic Exchange Service (DAAD), B. K. H. by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme, and A. T. S. by a grant from the Dutch Organization for Scientific Research (NWO; grant number 452-06-003). NR 68 TC 57 Z9 58 U1 3 U2 47 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2012 VL 22 IS 11 BP 2692 EP 2702 DI 10.1093/cercor/bhr352 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 018XH UT WOS:000309700700022 PM 22172578 ER PT J AU Murphy, M Kamin, H Masek, B Vogeli, C Caggiano, R Sklar, K Drubner, S Buonopane, R Picciotto, M Gold, J Jellinek, M AF Murphy, Michael Kamin, Hayley Masek, Bruce Vogeli, Christine Caggiano, Robert Sklar, Kenneth Drubner, Stacey Buonopane, Ralph Picciotto, Mark Gold, Joseph Jellinek, Michael TI Using brief clinician and parent measures to track outcomes in outpatient child psychiatry: longer term follow-up and comparative effectiveness SO CHILD AND ADOLESCENT MENTAL HEALTH LA English DT Article DE Child mental health; rating scales; outcomes measurement; comparative effectiveness ID PEDIATRIC SYMPTOM CHECKLIST; ASSESSMENT SCALE CGAS; HEALTH-CARE; PSYCHOSOCIAL PROBLEMS; QUALITY; SAMPLE; PSC-17; YOUTH AB Background: This study explored the feasibility and validity of using brief clinician- and parent-rated measures routinely over 6 months in outpatient child psychiatry. Method: All patients under 18 years of age seen for intake in the Child Psychiatry Clinic from 1 August 2007 through 31 July 2010 were eligible for inclusion in the study. Data were collected at intake for 1033 patients and at 3- and 6-month follow-up. Results: ANOVA for repeated measures showed statistically significant improvements in total and subscale scores on all three measures (Brief Psychiatric Rating Scale for Children, Childrens Global Assessment Scale, and Pediatric Symptom Checklist) at both second and third assessments. Conclusion: The fact that both broadband and narrowband scales showed significant improvements over the first 6 months of care establishes the possibility that these measures could be used in experimental designs studying comparative effectiveness. C1 [Murphy, Michael; Kamin, Hayley; Masek, Bruce; Jellinek, Michael] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Murphy, Michael; Masek, Bruce; Vogeli, Christine; Buonopane, Ralph; Gold, Joseph; Jellinek, Michael] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Vogeli, Christine] MGH Inst Hlth Policy, Boston, MA USA. [Caggiano, Robert] N Shore Med Ctr, Dept Psychiat, Salem, MA USA. [Sklar, Kenneth; Drubner, Stacey] Partners Psychiat & Mental Hlth, Boston, MA USA. [Buonopane, Ralph; Picciotto, Mark; Gold, Joseph] McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. [Jellinek, Michael] Newton Wellesley Hosp, Newton, MA USA. RP Murphy, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Yawkey 6A, Boston, MA 02114 USA. EM mmurphy6@partners.org RI Picciotto, Marina/F-8747-2012 OI Picciotto, Marina/0000-0002-4404-1280 NR 35 TC 1 Z9 1 U1 3 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1475-357X J9 CHILD ADOL MENT H-UK JI Child Adolesc. Ment. Health PD NOV PY 2012 VL 17 IS 4 BP 222 EP 230 DI 10.1111/j.1475-3588.2011.00642.x PG 9 WC Psychology, Clinical; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 023UX UT WOS:000310063000005 ER PT J AU Meng, R Dornbos, D Meng, L Wu, Y Liu, Y Li, GQ Li, GW Li, SJ Sun, F Wang, XY Ding, YC Ji, XM AF Meng, Ran Dornbos, David, III Meng, Lu Wu, Yan Liu, Yu Li, Guoqing Li, Guangwen Li, Sijie Sun, Fei Wang, Xiaoying Ding, Yuchuan Ji, Xunming TI Clinical differences between acute CVST and non-thrombotic CVSS SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE Cerebral venous sinus thrombosis; Cerebral venous sinus stenosis; D-Dimer; Fibrinogen; MRI/MRV; DSA ID IDIOPATHIC INTRACRANIAL HYPERTENSION; VENOUS-SINUS THROMBOSIS; D-DIMER LEVELS; PULMONARY-EMBOLISM; DIAGNOSIS; METAANALYSIS; EXCLUDE AB Background: Cerebral venous sinus thrombosis (CVST) is a rare stroke subtype, which has many overlapping symptoms with non-thrombotic cerebral venous sinus stenosis (CVSS) in the acute phase. Despite these similarities, their therapeutic regimens and outcomes are entirely different, and treatment delay is life-threatening. This study aims to address their clinical differences to help promote proper patient care. Methods: 34 cases of CVST and 34 cases of non-thrombotic CVSS diagnosed with digital subtraction angiography (DSA) in the acute phase (symptoms onset within 7 days) were consecutively enrolled in this prospective non-randomized and controlled study. Differences between CVST and CVSS in their clinical manifestation, plasma biomarkers, and MR or DSA imaging were compared. Results: CVST and CVSS overlap in many ways, but differ in their respective medical histories and neurological deficits. However, 20.6% of CVST and 64.7% of CVSS occur without a definitive medical history, and 70.6% of CVST and 64.7% of CVSS occur without focal neurologic deficits. In the acute phase of CVST, D-dimer and fibrinogen are found to be abnormally elevated in 94.1% and 73.5% of cases, respectively. In the CVSS group, D-dimer and fibrinogen are only elevated in 17.6% and 5.9% of cases, respectively (binary logistic regressions test, all P < 0.001). In the CVST group, the predominant features in MRI/MRV and DSA imaging include local brain lesions, flow void signal loss, non-visualization, and a local filling defect sign at the involved sinus. Conversely, in the CVSS group, imaging revealed symmetrically small bilateral ventricles and the spread of cerebral edema in MRI/MRV. DSA imaging in the CVSS group revealed external compression and a narrow sinus with disproportionate venous engorgement. Despite these findings, positive imaging only appears in a minority of patients in the two groups during the acute phase (Table 4). Conclusions: DSA may be beneficial to diagnose CVST in ambiguous patients suspected to have either CVST or CVSS. Clinically useful biomarkers (D-dimer and fibrinogen) may predict CVST in the emergency room in the ambiguous patients with or without equivocal MRI/MRV imaging. (c) 2012 Elsevier B.V. All rights reserved. C1 [Meng, Ran; Li, Guangwen; Li, Sijie; Sun, Fei; Ji, Xunming] Capital Med Univ, Xuanwu Hosp, China Amer Joint Inst Neurosci,Minist Educ, Cerebral Vasc Dis Res Inst,Key Lab Neurodegenerat, Beijing 100053, Peoples R China. [Meng, Ran; Liu, Yu; Li, Guoqing] Peking Univ, Clin Med Coll 9, Capital Med Univ, Beijing Shijitan Hosp,Dept Neurol, Beijing 100038, Peoples R China. [Dornbos, David, III; Ding, Yuchuan] Wayne State Univ, Sch Med, Dept Neurosurg, Detroit, MI USA. [Meng, Lu] Univ Georgia, Complex Carbohydrate Res Ctr, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ji, XM (reprint author), Capital Med Univ, Xuanwu Hosp, China Amer Joint Inst Neurosci,Minist Educ, Cerebral Vasc Dis Res Inst,Key Lab Neurodegenerat, 45 Changchun St, Beijing 100053, Peoples R China. EM jixm@ccmu.edu.cn FU National Natural Science Foundation [30770741]; Foundation of the Beijing High Level Health Systems Talented Technical Personnel Program [2009-03-02] FX This work was supported by the National Natural Science Foundation (30770741) and the Foundation of the Beijing High Level Health Systems Talented Technical Personnel Program (2009-03-02). NR 24 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD NOV PY 2012 VL 114 IS 9 BP 1257 EP 1262 DI 10.1016/j.clineuro.2012.03.036 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 024NJ UT WOS:000310115600011 PM 22676956 ER PT J AU Gao, HY Buist, DSM Lash, TL Bosco, JLF Swihart, B AF Gao, Hongyuan Buist, Diana S. M. Lash, Timothy L. Bosco, Jaclyn L. F. Swihart, Bruce TI Lasagna Plots Made in Different (Statistical) Ovens SO EPIDEMIOLOGY LA English DT Letter C1 [Gao, Hongyuan; Buist, Diana S. M.] Grp Hlth Res Inst, Seattle, WA USA. [Lash, Timothy L.] Aarhus Univ, Wake Forest Sch Med, Dept Clin Epidemiol, Dept Epidemiol & Prevent,Div Publ Hlth Sci, Aarhus, Denmark. [Swihart, Bruce] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Bosco, Jaclyn L. F.] Boston Med Ctr, Dana Farber Canc Inst, Boston, MA USA. RP Gao, HY (reprint author), Grp Hlth Res Inst, Seattle, WA USA. EM gao.h@ghc.org FU NCI NIH HHS [P01 CA154292, R01 CA093772, U01 CA063731] NR 5 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2012 VL 23 IS 6 BP 934 EP 934 DI 10.1097/EDE.0b013e31826d08c7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 022NJ UT WOS:000309965800033 PM 23038124 ER PT J AU Felker, GM Hasselblad, V Tang, WHW Hernandez, AF Armstrong, PW Fonarow, GC Voors, AA Metra, M McMurray, JJV Butler, J Heizer, GM Dickstein, K Massie, BM Atar, D Troughton, RW Anker, SD Califf, RM Starling, RC O'Connor, CM AF Felker, G. Michael Hasselblad, Vic Tang, W. H. Wilson Hernandez, Adrian F. Armstrong, Paul W. Fonarow, Gregg C. Voors, Adriaan A. Metra, Marco McMurray, John J. V. Butler, Javed Heizer, Gretchen M. Dickstein, Kenneth Massie, Barry M. Atar, Dan Troughton, Richard W. Anker, Stefan D. Califf, Robert M. Starling, Randall C. O'Connor, Christopher M. TI Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Troponin; Biomarkers; Heart failure ID CARDIAC TROPONIN; NATRIURETIC PEPTIDE; RISK STRATIFICATION; SERIAL CHANGES; MYOCARDIAL-INFARCTION; CLINICAL-IMPLICATIONS; OUTCOMES; NESIRITIDE; DIAGNOSIS AB We examined the prognostic importance of cardiac troponin I (cTnI) in a cohort of patients enrolled in the ASCEND-HF study of nesiritide in acute decompensated heart failure (ADHF). Circulating troponins are a prognostic marker in patients with ADHF. Contemporary assays with greater sensitivity require reassessment of the significance of troponin elevation in HF. Cardiac troponin I was measured in a core laboratory in 808 ADHF patients enrolled in the ASCEND-HF biomarkers substudy using a sensitive assay (VITROS Trop I ES, Ortho Clinical Diagnostics) with a lower limit of detection of 0.012 ng/mL and a 99th percentile upper reference limit (URL) of 0.034 ng/mL. Patients with clinical evidence of acute coronary syndrome or troponin 5 the URL were excluded. Multivariable modelling was used to assess the relationship between log(cTnI) and in-hospital and post-discharge outcomes. Baseline cTnI was undetectable in 22 and elevated above the 99th percentile URL in 50 of subjects. cTnI levels did not differ based on HF aetiology. After multivariable adjustment, higher cTnI was associated with worsened in-hospital outcomes such as length of stay (P 0.01) and worsening HF during the index hospitalization (P 0.01), but was not associated with worsened post-discharge outcomes at 30 or 180 days. The relationship between cTnI and outcomes was generally linear and there was no evidence of a threshold effect at any particular level of cTnI. cTnI is elevated above the 99th percentile URL in 50 of ADHF patients and predicts in-hospital outcome, but is not an independent predictor of long-term outcomes. C1 [Felker, G. Michael; Hasselblad, Vic; Hernandez, Adrian F.; Heizer, Gretchen M.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Tang, W. H. Wilson; Starling, Randall C.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Armstrong, Paul W.] Univ Alberta, Edmonton, AB, Canada. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Metra, Marco] Univ Brescia, Dept Cardiol, Brescia, Italy. [McMurray, John J. V.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. [Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Dickstein, Kenneth] Univ Bergen, Stavenger Univ Hosp, Bergen, Norway. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Atar, Dan] Univ Oslo, Ulleval Hosp, Dept Cardiol, N-0316 Oslo, Norway. [Atar, Dan] Univ Oslo, Inst Clin Med, N-0316 Oslo, Norway. [Troughton, Richard W.] Univ Otago, Christchurch, New Zealand. [Anker, Stefan D.] Charite, Dept Cardiol, D-13353 Berlin, Germany. [Anker, Stefan D.] IRCCS San Raffaele, Ctr Clin & Basic Res, Rome, Italy. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27705 USA. RP Felker, GM (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. EM Michael.felker@duke.edu RI Tang, Wai Hong/I-1238-2013; Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 FU Johnson Johnson; Roche Diagnostics; Critical Diagnostics; BG Medicine; Ortho Biotech FX Johnson & Johnson.; G.M.F.: research grants from Johnson & Johnson, Roche Diagnostics, Critical Diagnostics, and BG Medicine. A. F. H., K. D., J.J.,V.M., R. M. C., and C.M.O.: research grants from Johnson & Johnson. P. W. A.: research grants from Johnson & Johnson and Ortho Biotech. G. C. F. : consultant/advisory board for Scios and Novartis. A. A. V., J.B., and B. M. M.: consultant/advisory board for Johnson & Johnson. M. M.: consultant/advisory board for Corthera, Daiichi, Novartis, and Serrvier. R. W. T: consultant/advisory board for St. Jude Medical. S. D. A.: honoraria and consultant/advisory board for Alere Inc. (Europe), Thermo Fisher Scientific, and Vifor Pharma. R. C. S.: research support and consultant/advisory board for Johnson & Johnson. All other authors have no conflicts to declare. NR 25 TC 28 Z9 28 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2012 VL 14 IS 11 BP 1257 EP 1264 DI 10.1093/eurjhf/hfs110 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025EL UT WOS:000310168200010 PM 22764184 ER PT J AU Chatterjee, N Upadhyay, G Singh, J AF Chatterjee, Neal Upadhyay, Gaurav Singh, Jagmeet TI Meta-analysis of biventricular vs. right ventricular pacing mode in patients with atrial fibrillation undergoing atrioventricular nodal ablation: what was the quality of the included trials? - reply SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Letter ID CARDIAC RESYNCHRONIZATION THERAPY; RANDOMIZED CONTROLLED-TRIALS; JUNCTION ABLATION; HEART-FAILURE; DESIGN; SCALES C1 [Chatterjee, Neal; Upadhyay, Gaurav; Singh, Jagmeet] Massachusetts Gen Hosp, Dept Med, Boston, MA 02411 USA. [Chatterjee, Neal; Upadhyay, Gaurav; Singh, Jagmeet] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02411 USA. RP Chatterjee, N (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02411 USA. EM jsingh@partners.org NR 15 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2012 VL 14 IS 11 BP 1311 EP 1312 DI 10.1093/eurjhf/hfs149 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025EL UT WOS:000310168200017 ER PT J AU Harris, JR Burton, P Knoppers, BM Lindpaintner, K Bledsoe, M Brookes, AJ Budin-Ljosne, I Chisholm, R Cox, D Deschenes, M Fortier, I Hainaut, P Hewitt, R Kaye, J Litton, JE Metspalu, A Ollier, B Palmer, LJ Palotie, A Pasterk, M Perola, M Riegman, PHJ van Ommen, GJ Yuille, M Zatloukal, K AF Harris, Jennifer R. Burton, Paul Knoppers, Bartha Maria Lindpaintner, Klaus Bledsoe, Marianna Brookes, Anthony J. Budin-Ljosne, Isabelle Chisholm, Rex Cox, David Deschenes, Mylene Fortier, Isabel Hainaut, Pierre Hewitt, Robert Kaye, Jane Litton, Jan-Eric Metspalu, Andres Ollier, Bill Palmer, Lyle J. Palotie, Aarno Pasterk, Markus Perola, Markus Riegman, Peter H. J. van Ommen, Gert-Jan Yuille, Martin Zatloukal, Kurt TI Toward a roadmap in global biobanking for health SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DATASHAPER APPROACH; TRANSLATION; BIOMARKERS; DATABASES; MEDICINE; GENOMICS; QUALITY; SOCIETY; SCIENCE; ETHICS AB Biobanks can have a pivotal role in elucidating disease etiology, translation, and advancing public health. However, meeting these challenges hinges on a critical shift in the way science is conducted and requires biobank harmonization. There is growing recognition that a common strategy is imperative to develop biobanking globally and effectively. To help guide this strategy, we articulate key principles, goals, and priorities underpinning a roadmap for global biobanking to accelerate health science, patient care, and public health. The need to manage and share very large amounts of data has driven innovations on many fronts. Although technological solutions are allowing biobanks to reach new levels of integration, increasingly powerful data-collection tools, analytical techniques, and the results they generate raise new ethical and legal issues and challenges, necessitating a reconsideration of previous policies, practices, and ethical norms. These manifold advances and the investments that support them are also fueling opportunities for biobanks to ultimately become integral parts of health-care systems in many countries. International harmonization to increase interoperability and sustainability are two strategic priorities for biobanking. Tackling these issues requires an environment favorably inclined toward scientific funding and equipped to address socio-ethical challenges. Cooperation and collaboration must extend beyond systems to enable the exchange of data and samples to strategic alliances between many organizations, including governmental bodies, funding agencies, public and private science enterprises, and other stakeholders, including patients. A common vision is required and we articulate the essential basis of such a vision herein. European Journal of Human Genetics (2012) 20, 1105-1111; doi:10.1038/ejhg. 2012.96; published online 20 June 2012 C1 [Harris, Jennifer R.; Budin-Ljosne, Isabelle] Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, N-0403 Oslo, Norway. [Burton, Paul; Brookes, Anthony J.] Univ Leicester, Leicester, Leics, England. [Burton, Paul; Deschenes, Mylene; Fortier, Isabel] Publ Populat Project Genom P3G, Montreal, PQ, Canada. [Knoppers, Bartha Maria] McGill Univ, Ctr Genom & Policy, Montreal, PQ, Canada. [Lindpaintner, Klaus] SDIX Inc, Newark, NJ USA. [Lindpaintner, Klaus] Lindpaintner Biobanks Consulting, Muttenz, Switzerland. [Bledsoe, Marianna] US Dept Vet Affairs, Washington, DC USA. [Chisholm, Rex] Northwestern Univ, Sch Med, Ctr Genet Med, Chicago, IL USA. [Cox, David] Pfizer Inc, Biotherapeut & Bioinnovat Ctr, San Francisco, CA USA. [Fortier, Isabel] McGill Univ, Ctr Hlth, Res Inst, Montreal, PQ, Canada. [Hainaut, Pierre; Pasterk, Markus] Int Prevent Res Inst, Lyon, France. [Hewitt, Robert] European Middle Eastern & African Soc Biopreserva, Marseille, France. [Kaye, Jane] Univ Oxford, Dept Publ Hlth, Ctr Hlth Law & Emerging Technol, Oxford, England. [Litton, Jan-Eric] Karolinska Inst, Stockholm, Sweden. [Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Ollier, Bill] Univ Manchester, Manchester Acad Hlth Sci Ctr, Ctr Integrated Genom Med Res, Manchester, Lancs, England. [Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Palmer, Lyle J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Palotie, Aarno] Wellcome Trust Sanger Inst, Hinxton, S Cambs, England. [Palotie, Aarno] Univ Helsinki, Helsinki, Finland. [Palotie, Aarno] Broad Inst MIT & Harvard, Cambridge, MA USA. [Perola, Markus] Natl Inst Hlth & Welf, Helsinki, Finland. [Riegman, Peter H. J.] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Human & Clin Genet, Leiden, Netherlands. [van Ommen, Gert-Jan] Ctr Med Syst Biol, Leiden, Netherlands. [Zatloukal, Kurt] Med Univ Graz, Graz, Austria. RP Harris, JR (reprint author), Norwegian Inst Publ Hlth, Dept Genes & Environm, Div Epidemiol, Post Box 4404 Nydalen, N-0403 Oslo, Norway. EM Jennifer.harris@fhi.no RI Palmer, Lyle/K-3196-2014; Hainaut, Pierre /B-6018-2012; Burton, Paul/H-7527-2016; Pasterk, Markus/A-6588-2011 OI Palmer, Lyle/0000-0002-1628-3055; Hainaut, Pierre /0000-0002-1303-1610; Yuille, Martin/0000-0002-4992-5405; Budin-Ljosne, Isabelle/0000-0002-4610-1662; Pasterk, Markus/0000-0002-6127-3323 FU European Union's Seventh Framework Programme (FP7); ENGAGE Consortium [HEALTH-F4-2007-201413]; BioSHaRE-EU [HEALTH-F4-2010-261433]; Biobank Norway - a national infrastructure for biobanks and biobank-related activity in Norway; Norwegian Research Council [NFR 197443/F50]; Public Population Project in Genomics (P3G) and biobanking-related work from FP7 Grant [212111]; Austrian Genome Programme GEN-AU; Canada Research Chair in Law and Medicine; Genome Canada/Genome Quebec GJBvO; Ministry of Education; Netherlands Organization for Scientific Research NWO for the establishment of BBMRI-NL; Netherlands Biobanking infrastructure; Swedish Research Council Grant [8292009-6285]; EU RDF Centre of Excellence in Genomics; The Estonian Biobank at EGC University of Tartu; Ministry of Social Affairs and Ministry of Education and Research and EU FP7 project OPENGENE; Wellcome Trust [096599/2/11/Z]; The Medical Research Council (UDBN, COPDmap); IMI (U-biopred); Technology Strategy Board (STRATUM, ACROPOLIS); The Medical Research Council (COPDmap) EU FP7; GEN2PHEN [200754] FX This work was supported through funds from the European Union's Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007-201413 to JRH and IBL; BioSHaRE-EU, grant agreement HEALTH-F4-2010-261433 to JRH, PB, AJB, and IBL; through funds from Biobank Norway - a national infrastructure for biobanks and biobank-related activity in Norway - funded by the Norwegian Research Council (NFR 197443/F50) to JRH and IBL. We thank the contribution of the Public Population Project in Genomics (P3G) and biobanking-related work from FP7 Grant Agreement number: 212111 (BBMRI) to KZ, and MY, and the Austrian Genome Programme GEN-AU to KZ. BMK acknowledges the Canada Research Chair in Law and Medicine; Genome Canada/Genome Quebec GJBvO gratefully acknowledges support by a grant from the Ministry of Education, through the Netherlands Organization for Scientific Research NWO for the establishment of BBMRI-NL, a consolidated Netherlands Biobanking infrastructure. JEL gratefully acknowledges support by The Swedish Research Council Grant agreement 8292009-6285 for the BBMRI. SE project. AM was supported by EU RDF Centre of Excellence in Genomics; The Estonian Biobank at EGC University of Tartu is funded by Ministry of Social Affairs and Ministry of Education and Research and EU FP7 project OPENGENE. Other sources of support for this work are the Wellcome Trust 096599/2/11/Z to JK, The Medical Research Council (UDBN, COPDmap), IMI (U-biopred) and Technology Strategy Board (STRATUM, ACROPOLIS) to MY, and The Medical Research Council (COPDmap) EU FP7 and (GEN2PHEN (Grant # 200754) to AJB. NR 40 TC 57 Z9 59 U1 1 U2 25 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD NOV PY 2012 VL 20 IS 11 BP 1105 EP 1111 DI 10.1038/ejhg.2012.96 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 025TW UT WOS:000310218600002 PM 22713808 ER PT J AU Lionetto, L Negro, A Casolla, B Simmaco, M Martelletti, P AF Lionetto, Luana Negro, Andrea Casolla, Barbara Simmaco, Maurizio Martelletti, Paolo TI Sumatriptan succinate: pharmacokinetics of different formulations in clinical practice SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Editorial Material DE acute migraine; drug formulation; pharmacodynamics; pharmacokinetics; sumatriptan succinate ID MENSTRUALLY RELATED MIGRAINE; EPISODIC CLUSTER HEADACHE; PAIN-FREE EFFICACY; SUBCUTANEOUS SUMATRIPTAN; NASAL SPRAY; DOUBLE-BLIND; ORAL SUMATRIPTAN; OPEN-LABEL; INTRANASAL SUMATRIPTAN; HEALTHY-VOLUNTEERS AB Introduction: Migraine is a common neurovascular disorder characterized by recurrent episodes of disabling headache, autonomic nervous system dysfunction, and in some patients, neurological aura symptoms. Triptans are frequently prescribed drugs for the treatment of the acute migraine attack, considering their capability to provide wide efficacy and tolerability. Areas covered: This review discusses pharmacodynamics and pharmacokinetics of sumatriptan succinate, considering the clinical impact of new drug formulations in the treatment of acute migraine and cluster headache. The data were obtained by searching the following keywords in MEDLINE: sumatriptan succinate, pharmacokinetics, pharmacodynamics, triptans, migraine, new delivery systems, relative to the period 1989 - 2012. Expert opinion: Subcutaneous sumatriptan has been considered as the most efficacious treatment in the acute phase of migraine both on pain alone as well as on associated autonomic symptoms. Pharmacologically, pharmacokinetic parameters, in particular bioavailability, T-max and C-max are responsible for the wide efficacy of the compound and the limited adverse effect (AE) profile. The new drug formulations that are the most similar to the pharmacokinetics parameters of the subcutaneous one are promising because they both improve pharmacokinetic bioavailability bypassing the first-pass metabolism and increase patient compliance. C1 [Negro, Andrea; Martelletti, Paolo] Univ Roma La Sapienza, Reg Referral Headache Ctr, Dept Clin & Mol Med, I-00189 Rome, Italy. [Lionetto, Luana; Casolla, Barbara; Simmaco, Maurizio] Univ Roma La Sapienza, St Andrea Hosp, NESMOS Dept, Adv Mol Diagnost Unit, I-00189 Rome, Italy. [Negro, Andrea] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Stroke & Neurovasc Regulat, Boston, MA 02115 USA. RP Martelletti, P (reprint author), Univ Roma La Sapienza, Reg Referral Headache Ctr, Dept Clin & Mol Med, Via Grottarossa 1035, I-00189 Rome, Italy. EM paolo.martelletti@uniroma1.it RI Lionetto, Luana/J-3632-2016 OI Lionetto, Luana/0000-0002-5272-6642 NR 99 TC 13 Z9 13 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD NOV PY 2012 VL 13 IS 16 BP 2369 EP 2380 DI 10.1517/14656566.2012.730041 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 022EM UT WOS:000309938400009 PM 23013035 ER PT J AU Townamchai, K Lee, L Viswanathan, AN AF Townamchai, Kanokpis Lee, Larissa Viswanathan, Akila N. TI A novel low dose fractionation regimen for adjuvant vaginal brachytherapy in early stage endometrioid endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT World Congress of Brachytherapy CY MAY 10-12, 2012 CL Barcelona, SPAIN DE Endometrial cancer; Vaginal brachytherapy; High-dose-rate ID EXTERNAL-BEAM RADIOTHERAPY; INTRAVAGINAL BRACHYTHERAPY; AMERICAN BRACHYTHERAPY; VAULT BRACHYTHERAPY; RANDOMIZED-TRIAL; CARCINOMA; INTERMEDIATE; IRRADIATION; ADENOCARCINOMA; RADIATION AB Purpose. To evaluate local control, survival and toxicity in patients with early-stage endometrioid adenocarcinoma of the uterus treated with adjuvant high-dose-rate (HDR) vaginal brachytherapy (VB) alone using a novel low dose regimen. Methods. We reviewed records of 414 patients with stage IA to stage II endometrial adenocarcinoma treated with VB alone from 2005 to 2011. Of these, 157 patients with endometrioid histology received 24 Gy in 6 fractions of HDR vaginal cylinder brachytherapy and constitute the study population. Dose was prescribed at the cylinder surface and delivered twice weekly in the post-operative setting. Local control and survival rates were calculated by the Kaplan-Meier method. Results. All 157 patients completed the prescribed course of VB. Median follow-up time was 22.8 months (range, 1.5-76.5). Two patients developed vaginal recurrence, one in the periurethral region below the field and one in the fornix after treatment with a 2.5-cm cylinder. Three patients developed regional recurrence in the para-aortic region. Two patients developed distant metastasis (lung and carcinomatosis). The 2-year rate of vaginal control was 98.6%. locoregional control was 97.9% and disease-free survival was 96.8%. The 2-year overall survival rate was 98.7%. No Grade 2 or higher vaginal, gastrointestinal, genitourinary or skin long-term toxicity was reported for any patient. Conclusion. Vaginal brachytherapy alone in early-stage endometrial cancer provides excellent results in terms of locoregional control and disease-free survival. The fractionation scheme of 24 Gy in 6 fractions prescribed to the cylinder surface was well-tolerated with minimal late toxicity. (C) 2012 Elsevier Inc. All rights reserved. C1 [Townamchai, Kanokpis; Lee, Larissa; Viswanathan, Akila N.] Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NCI NIH HHS [K07 CA117979] NR 25 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2012 VL 127 IS 2 BP 351 EP 355 DI 10.1016/j.ygyno.2012.07.111 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 024GN UT WOS:000310097800017 PM 22850411 ER PT J AU Wang, JH Reinherz, EL AF Wang, Jia-huai Reinherz, Ellis L. TI The structural basis of a ss T-lineage immune recognition: TCR docking topologies, mechanotransduction, and co-receptor function SO IMMUNOLOGICAL REVIEWS LA English DT Review DE T-cell receptor; adaptive immunity; CD4; CD8; structural immunology; mechanoreceptor ID MAJOR HISTOCOMPATIBILITY COMPLEX; CELL ANTIGEN RECEPTOR; BETA FG LOOP; THORACIC DUCT LYMPHOCYTES; HEMOLYSIN-FORMING CELLS; CLASS-I INTERACTION; MHC CLASS-II; CRYSTAL-STRUCTURE; PEPTIDE-MHC; THYMIC SELECTION AB Self versus non-self discrimination is at the core of T-lymphocyte recognition. To this end, a beta T-cell receptors (TCRs) ligate foreign peptides bound to major histocompatibility complex (MHC) class I or class II molecules (pMHC) arrayed on the surface of antigen-presenting cells (APCs). Since the discovery of TCRs approximately 30 similar to years ago, considerable structural and functional data have detailed the molecular basis of their extraordinary ligand specificity and sensitivity in mediating adaptive T-cell immunity. This review focuses on the structural biology of the Fab-like TCRa beta clonotypic heterodimer and its unique features in conjunction with those of the associated CD3e? and CD3ed heterodimeric molecules, which, along with CD3?? homodimer, comprise the TCR complex in a stoichiometry of 1:1:1:1. The basis of optimized TCRa beta docking geometry on the pMHC linked to TCR mechanotransduction and required for T-cell signaling as well as CD4 and CD8 co-receptor function is detailed. A model of the TCR ectodomain complex including its connecting peptides suggests how force generated during T-cell immune surveillance and at the immunological synapse results in dynamic TCR quaternary change involving its heterodimeric components. Potential insights from the structural biology relevant to immunity and immunosuppression are revealed. C1 [Wang, Jia-huai; Reinherz, Ellis L.] Dana Farber Canc Inst, Immunol Lab, Boston, MA 02115 USA. [Wang, Jia-huai; Reinherz, Ellis L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wang, Jia-huai; Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunol Lab, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU US NIH FX This work was supported by research grants from US NIH to ELR and J-HW. The authors have no conflict of interest to declare. NR 120 TC 32 Z9 32 U1 3 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD NOV PY 2012 VL 250 SI SI BP 102 EP 119 DI 10.1111/j.1600-065X.2012.01161.x PG 18 WC Immunology SC Immunology GA 019PR UT WOS:000309752300007 PM 23046125 ER PT J AU Strymish, J Branch-Elliman, W Itani, KMF Williams, S Gupta, K AF Strymish, Judith Branch-Elliman, Westyn Itani, Kamal M. F. Williams, Sandra Gupta, Kalpana TI A Clinical History of Methicillin-Resistant Staphylococcus aureus Is a Poor Predictor of Preoperative Colonization Status and Postoperative Infections SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID CARRIAGE; VETERANS; MRSA AB OBJECTIVE. In the absence of established methicillin-resistant Staphylococcus aureus (MRSA) screening programs, many centers use a history of a positive culture or a nasal screen as a surrogate for preoperative MRSA colonization status. We aimed to evaluate the test characteristics of these surrogates. DESIGN. Retrospective cohort study. PARTICIPANTS. Veterans Affairs Boston Healthcare System surgical patients with a preoperative nasal MRSA polymerase chain reaction (PCR) screen. METHODS. We assessed the performance of a history of a MRSA-positive culture or a positive nasal MRSA PCR screen during the year prior to surgery for predicting the preoperative nasal PCR screen result. The associations between MRSA history and postoperative outcomes, including MRSA cultures and infections, were also evaluated. RESULTS. Among 4,238 patients, a positive MRSA culture history had a sensitivity of 19.7% (95% confidence interval [CI], 15.4%-24.8%) and positive predictive value of 57.3% for the preoperative nasal MRSA status. The specificity of MRSA culture history was 99% (95% CI, 98.5%-99.2%). Prior-year nasal MRSA screen results had similar test characteristics. A history of a MRSA-positive culture was associated with an increased risk of postoperative MRSA-positive cultures (risk ratio [RR], 3.54 [95% CI, 1.70-7.37], P < .001) but not of infections (RR, 1.71 [95% CI, 0.58-5.01]), after adjustment for preoperative nasal MRSA status, vancomycin surgical prophylaxis, surgical scrub, and age. CONCLUSIONS. A history of a MRSA-positive culture and a positive nasal PCR screen are poor surrogate markers of preoperative colonization status, missing at least 70% of MRSA-colonized patients. Prior-year history is also not independently associated with MRSA-related postoperative infections. Strong consideration should be given to preoperative MRSA screening in patients at high risk for surgical complications. C1 [Strymish, Judith; Gupta, Kalpana] Vet Affairs Boston Healthcare Syst, Dept Med, Boston, MA USA. [Strymish, Judith; Itani, Kamal M. F.] Harvard Univ, Sch Med, Boston, MA USA. [Branch-Elliman, Westyn] Beth Israel Deaconess Med Ctr, Dept Med & Hosp Epidemiol, Boston, MA 02215 USA. [Itani, Kamal M. F.] Vet Affairs Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Itani, Kamal M. F.; Gupta, Kalpana] Boston Univ, Sch Med, Boston, MA 02118 USA. [Williams, Sandra] Vet Affairs Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. RP Gupta, K (reprint author), VA Boston HCS, 1400 VFW Pkwy, Boston, MA 02132 USA. EM kalpana.gupta@va.gov OI Branch-Elliman, Westyn/0000-0002-9658-5124 FU Merck Pharmaceuticals; Trius Pharmaceuticals FX K.F.I. reports that he has received research support for other studies from Merck Pharmaceuticals and Trius Pharmaceuticals and has served as an advisor to Forest Pharmaceuticals. All other authors report no conflicts of interest relevant to this article. All authors submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest, and the conflicts that the editors consider relevant to this article are disclosed here. NR 16 TC 3 Z9 3 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2012 VL 33 IS 11 BP 1113 EP 1117 DI 10.1086/668026 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 018MU UT WOS:000309665800008 PM 23041809 ER PT J AU Kamboj, M Son, C Cantu, S Chemaly, RF Dickman, J Dubberke, E Engles, L Lafferty, T Liddell, G Lesperance, ME Mangino, JE Martin, S Mayfield, J Mehta, SA O'Rourke, S Perego, CS Taplitz, R Eagan, J Sepkowitz, KA AF Kamboj, Mini Son, Crystal Cantu, Sherry Chemaly, Roy F. Dickman, Jeanne Dubberke, Erik Engles, Lisa Lafferty, Theresa Liddell, Gale Lesperance, Mary Ellen Mangino, Julie E. Martin, Stacy Mayfield, Jennie Mehta, Sapna A. O'Rourke, Susan Perego, Cheryl S. Taplitz, Randy Eagan, Janet Sepkowitz, Kent A. TI Hospital-Onset Clostridium difficile Infection Rates in Persons with Cancer or Hematopoietic Stem Cell Transplant: A C3IC Network Report SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID DISEASE AB A multicenter survey of 11 cancer centers was performed to determine the rate of hospital-onset Clostridium difficile infection (HO-CDI) and surveillance practices. Pooled rates of HO-CDI in patients with cancer were twice the rates reported for all US patients (15.8 vs 7.4 per 10,000 patient-days). Rates were elevated regardless of diagnostic test used. C1 [Kamboj, Mini; Son, Crystal; Eagan, Janet; Sepkowitz, Kent A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Lafferty, Theresa] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Liddell, Gale] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Martin, Stacy] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Cantu, Sherry; Chemaly, Roy F.; Perego, Cheryl S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Dubberke, Erik; Mayfield, Jennie] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Dickman, Jeanne; Mangino, Julie E.] Ohio State Univ, Med Ctr, James Canc Hosp, Columbus, OH 43210 USA. [O'Rourke, Susan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Engles, Lisa; Lesperance, Mary Ellen] Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Taplitz, Randy] UCSD, Thornton Hosp, La Jolla, CA USA. [Mehta, Sapna A.] NYU, Langone Med Ctr, New York, NY USA. [Dubberke, Erik] Washington Univ, Sch Med, St Louis, MO USA. RP Kamboj, M (reprint author), 1275 York Ave, New York, NY 10065 USA. EM kambojm@mskcc.org OI KAMBOJ, MINI/0000-0002-3122-6374 FU NIH/NIAID [K23-AI0838880] FX M.K. was supported by NIH/NIAID grant K23-AI0838880. NR 9 TC 21 Z9 22 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2012 VL 33 IS 11 BP 1162 EP 1165 DI 10.1086/668023 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 018MU UT WOS:000309665800017 PM 23041818 ER PT J AU Chiu, CY Gomolka, B Dierkes, C Huang, NR Schroeder, M Purschke, M Manstein, D Dangi, B Weylandt, KH AF Chiu, Cheng-Ying Gomolka, Beate Dierkes, Cordula Huang, Nora R. Schroeder, Maik Purschke, Martin Manstein, Dieter Dangi, Bindi Weylandt, Karsten H. TI Erratum to: Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis SO INFLAMMATION RESEARCH LA English DT Correction C1 [Weylandt, Karsten H.] Charite Campus Virchow Hosp, Med Klin MS Gastroenterol & Hepatol, D-13353 Berlin, Germany. [Chiu, Cheng-Ying; Gomolka, Beate; Dierkes, Cordula; Huang, Nora R.; Schroeder, Maik; Weylandt, Karsten H.] Charite, Dept Hepatol Gastroenterol & Endocrinol, Campus Virchow Klinikum, D-13353 Berlin, Germany. [Chiu, Cheng-Ying; Huang, Nora R.; Weylandt, Karsten H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol, Boston, MA USA. [Purschke, Martin; Manstein, Dieter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Dangi, Bindi] DSM Nutr Prod, Columbia, MD USA. RP Weylandt, KH (reprint author), Charite Campus Virchow Hosp, Med Klin MS Gastroenterol & Hepatol, Augustenburger Pl 1, D-13353 Berlin, Germany. EM karsten.weylandt@charite.de NR 1 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD NOV PY 2012 VL 61 IS 11 BP 1293 EP 1293 DI 10.1007/s00011-012-0552-5 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 021FW UT WOS:000309871700015 ER EF